









































CRISPR and COVID-19: Lessons 
Learned to Prepare for the Next 

Pathogen 
James M. Bond

Volume Two
Edition One
Fall 2021

 
GEORGETOWN SCIENTIFIC
RESEARCH JOURNAL

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CRISPR and COVID-19: Lessons Learned to Prepare for the 
Next Pathogen 
 
James M. Bond 
 
Department of Science, Technology, and International Affairs, Georgetown University, Washington, D.C., 
United States. 
E-mail: jmb516@georgetown.edu 
https://doi.org/10.48091/gsr.v2i1.29  

Abstract 

CRISPR-Cas is a gene editing technology that can strengthen a defense countermeasure against an 
infectious pathogen and can heighten the attack risk of an engineered pathogen. The purpose of this report 
is twofold: to analyze the advantages of CRISPR for participants within a strategic environment, such as 
rogue, non-state attackers and defenders coordinated between nation-states and other entities, and to 
identify the ways in which CRISPR configures a defender’s countermeasure against a biological event. In 
its assessment, this report utilizes the case study of COVID-19 to examine the applications of CRISPR-
Cas systems to SARS-CoV-2. This report finds that CRISPR reduces some barriers to entry and 
exacerbates the possibility for malicious non-state attackers to engineer a pathogen and engender a serious 
biological event in the very short-term. However, key barriers to entry will continue to pose challenges to 
attackers comparative to defenders. In this report, “attacker” refers to non-state actors maliciously using 
CRISPR to engender a biological event while “defender” refers to coordinated entities responding to 
biological events, whether natural or deliberate. In the short- to mid-term, the use of CRISPR-Cas 
systems in designing a countermeasure against a biological event is to the advantage of the defender. 
CRISPR offers more accessible, rapid, and convenient diagnostic testing; a quick and accurate platform 
to identify viral vectors; and the potential for antiviral therapy. Through enactment of certain policy 
configurations, the comparative advantage of CRISPR may decisively shift to the defender, including in 
the very short-term. 

Keywords: COVID-19, CRISPR, Biosecurity, Dual-Use Risk Technology

1. Introduction 

 In December of 2019, a novel coronavirus, now 
known as SARS-CoV-2, was identified in 
Wuhan, China.1 The disease caused by this virus – 
Coronavirus disease 19 (COVID-19) – spread 
throughout the world and was eventually 
characterized as a pandemic by the World Health 
Organization (WHO).2 From the first cases in 
China to the ongoing pandemic, COVID-19 has 
presented major challenges to economies, 

governments, health systems, and communities 
everywhere. As of August 20th, 2021, over 
200,000,000 cases have been reported and 
4,300,000 deaths have been attributed to COVID-
19, according to the WHO.3  

On December 2, 2020, the first fully tested 
immunization was approved for use.4 Various 
other tested immunizations were approved across 
the globe shortly after. At this time, around 
4,850,000,000 vaccines have been administered, 

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according to the Center for Systems Science and 
Engineering (CSSE) at Johns Hopkins 
University.5 However, waves of COVID-19 cases 
continue to rise in several countries, especially due 
to highly transmissible variants and insufficient 
population immunity.6, 7 Furthermore, due to an 
immense scope of global vaccine inequity, a 
majority of low- and lower-middle-income 
countries may continue to experience surges in 
COVID-19 cases for years to come.8 These facts 
drive continued public health measures for 
countries, as they denote that the COVID-19 
pandemic is not over.  

The imperative to constrain this virus 
motivated countries to take innovative defense 
measures against COVID-19. Among these 
innovative applications was a gene editing 
technology that was discovered in the 2010s and is 
based on natural bacterial immune mechanisms 
against viruses called CRISPR-Cas systems.9 The 
systems are composed of two components: a guide 
RNA that identifies a target gene and a CRISPR-
associated protein that can cut double stranded 
DNA, allowing for site-specific genome 
modification that is quick, cheap, and relatively 
user-friendly.10 Researchers are now faced with 
deciding how best to optimize the system for 
human applications, and the COVID-19 
pandemic presented a myriad of pressing public 
health challenges that CRISPR could help 
mitigate.  

Simultaneously, CRISPR gene editing 
technology has the potential to be abused for 
malicious applications to the opposite effect of 
aiding public health responses. Specifically, 
CRISPR is often touted for its comparative ease of 
use and efficiency in editing genes,11 which could 
present the opportunity for malicious attackers to 
genetically engineer pathogens into a biological 
weapon. As CRISPR reduces barriers of entry due 
to its low cost and ease of use, more attackers could 

use CRISPR to cause a deliberate biological event 
(DBE). 

This report will analyze the advantages 
CRISPR holds for the attacker and defender, as 
well as how the technology can be leveraged to 
configure a countermeasure against biological 
events to enhance global biopreparedness. 
Utilizing CRISPR during the COVID-19 
pandemic represents expanded use of a novel 
technology for a public health crisis. This report 
will begin by examining the risk factors that 
malicious non-state attackers utilizing CRISPR 
and other developing phenomena pose for the 
strategic environment. The report will then move 
to the application of CRISPR from three principal 
areas: COVID-19 diagnostic tests, pathogenic 
research, and the potential of antiviral therapy. 
Finally, the report will draw conclusions pertaining 
to the global health strategic environment and 
recommend policy to bolster global 
biopreparedness.  

In this report, “non-state malicious attacker”, 
or “attacker”, refers to rogue groups or individuals 
utilizing CRISPR with malicious intent to 
engender a biological event. The term “biological 
event” refers to an outbreak of a disease caused by 
a pathogen and can be naturally occurring or 
deliberately released.12 “Defender” refers to the 
coordinated entities responding to a natural or 
deliberate biological event, including, but not 
limited to, governments, the scientific community, 
institutions, and sectors. “Biopreparedness” refers 
to a state of readiness a defender builds for 
potential biological events.13 The “strategic 
environment” is defined as the complex interaction 
of entities such as “attackers” and “defenders” amid 
dynamic and contradictory global forces.14 
“Pathogenic surveillance regime” refers to a 
coordinated program to survey and curtail the 
infectious progression of a pathogen within a 
society, usually directed by a government. 

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2. Anticipating the threat of CRISPR engineered 
pathogens 

 CRISPR-Cas systems can be utilized to delete 
genetic sequences, add genetic sequences, regulate 
expression of a phenotype, and even combine 
genetic sequences to produce a novel expression.15 
CRISPR-Cas systems are democratized for use, as 
gene editing kits are commercially available from 
laboratory suppliers and genome engineering 
companies and are relatively inexpensive. 
Furthermore, CRISPR technologies – especially 
these gene editing kits – are touted for their ease-
of-use compared to other techniques for genomic 
manipulation.15 However, the same accessibility, 
low cost, and ease-of-use of CRISPR-Cas could 
greatly expand the scope of potential users. In 
many ways, it is a boon for positive biological 
applications, and research in the field has 
flourished due to the democratization of gene 
editing. In other ways, the technology could pose 
a biosecurity risk if applied to malicious genomic 
engineering, rendering it a dual use research of 
concern. That is, research that advances our 
understanding of CRISPR-Cas has the potential 
to be directly misapplied and pose a biological 
threat.  

Regardless of the numerous positive 
applications, CRISPR could open the door for 
malicious non-state attackers to engineer 
optimized pathogenic bioweapons. Prior genomic 
manipulation techniques posed significant barriers 
of entry, requiring resources and scientific 
expertise for performing expensive and complex 
biological procedures such as constructing zinc-
finger arrays or delivering gene editing materials 
into cells.16, 17 CRISPR-Cas systems circumvent 
some of the impediments apparent in other 
methods like TALENs (Transcription activator-
like effector nucleases) or zinc fingers. In fact, the 
concerns that the broad distribution and low cost 
of the technology increase the risk for deliberate 
misuse were stressed in multiple US Intelligence 

Community threat assessments.18, 19 These 
advances in gene editing highlight the modern 
reality that the tools necessary for genetically 
engineering a dangerous pathogen are increasingly 
available, and the biosecurity risk for a DBE could 
be greater now than ever before. Though potential 
targets of maliciously released pathogens are 
diverse,20 for practicality in this report, discussion 
regarding the threat of an engineered pathogen 
refers to that targeting humans. 

Beyond the reduced barrier of entry for 
engineering a pathogen, the attacker may also have 
certain advantages in releasing that pathogen and 
causing a DBE. Although there may be several 
similarities between the defense countermeasure 
against either a deliberate or natural biological 
event, a DBE may introduce additional 
requirements for several factors, from responder 
safety to attacker attribution.21 The determination 
of natural or deliberate origin would presumably be 
made by a coordinated effort of stakeholders from 
intelligence communities and clinical professionals 
with standard criteria for assessing the biological 
event.22 However, upon identification of a DBE, it 
still may prove difficult to discern whether this 
intentional release is a wild-type or genetically 
engineered pathogen, which is crucial information 
for assessing pathogenesis due to environment and 
natural selection. That is to say, genetically 
engineered pathogens may experience a 
comparatively more rapid process of change in 
selecting for new genes that make the pathogen 
more competitive while suppressing other genes 
that are metabolically expensive.23 A dynamic 
pathogen like this may confound an efficient 
countermeasure from the defender. Furthermore, 
convoluted dimensions and numerous 
stakeholders in a public health response may 
inhibit an efficient countermeasure by the 
defender. A proactive release of a pathogen by an 
attacker is fundamentally less complicated than a 
reactive response by a defender.   

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Understanding the complex field of genetics 
for beneficial human applications  is a problem 
facing researchers in CRISPR for today. From 
pleiotropic effects where one gene can have 
multiple expressions to epigenetic effects where 
expression is regulated by environmental factors, a 
limitation of CRISPR gene editing is scientific 
understanding of how genes are associated with 
specific phenotypic expressions. After all, 
CRISPR is most often and easily utilized in order 
to silence genes to create new phenotypes rather 
than add genes to create new phenotypes because 
of these limitations in scientific understanding. 
Furthermore, some have cited the fact that the 
notable studies utilizing CRISPR are conducted 
by the most well-resourced and important labs, 
suggesting that CRISPR still requires a significant 
level of expertise in order to effectively operate the 
technology for complicated uses. 24 Thus, the 
barriers of entry of scientific understanding and a 
certain level of expertise remains for attackers. As 
a genetically engineered pathogen is released, it 
may have unpredictable and unintended effects, 
again due to environment and natural selection. 
For instance, an optimized pathogen could be 
engineered with the intent for higher transmission 
and lethality and be presumed by the attacker to 
cause a catastrophic DBE yet perform 
unpredictably when released because it kills the 
human host too efficiently to replicate and 
spread.24 This theoretical example would 
unintentionally underperform the attacker’s goals. 
Furthermore, the delivery mechanism to 
weaponize a biological agent has classically been a 
limiting factor for malicious use.21 (p. 90) This too 
remains as a limiting barrier of entry for 
contemporary attackers, particularly if the desired 
release is within a mass population.  

Some barriers of entry persist for the attacker. 
Even so, a release of a genetically engineered 
pathogen that exhibits characteristics unintended 
by the attacker can still be problematic for the 

defender. If the attacker can surmount these 
barriers of knowledge and delivery, while 
harnessing the low cost and ease of use of 
CRISPR, a resulting DBE may be devastating to 
the defender. Therefore, it is critically important 
to bolster global biopreparedness in both 
prevention and reaction strategies. For example, 
monitoring supply chains of CRISPR kits and 
dangerous pathogenic sequences may be 
worthwhile. However, it seems apparent that not 
all biological attacks may be preventable due to the 
lowered barriers of access to gene editing as well as 
the difficulty of surveillance over genetic and 
CRISPR materials. Thus, for the remainder of the 
report, there will be a primary focus on the reaction 
of the defender, but this is not meant to discount 
the need for rethought prevention strategies. In the 
instances of a devastating DBE, an expeditious, 
prepared response to contain the spread of the 
pathogen should be a foremost consideration. 

3. CRISPR Applications to the COVID-19 
pandemic 

 This report finds that CRISPR-Cas systems 
can be leveraged to configure an effective 
countermeasure against a natural or deliberate 
biological event, particularly in terms of rapidity 
and feasibility of response. In the case study of 
CRISPR use in the COVID-19 public health 
response, three principal applications prevail: 
diagnostics, research, and potential antiviral 
therapy. CRISPR diagnostic platforms can 
provide accessible, rapid, and convenient tests, 
without sacrificing standards of accuracy. 
CRISPR-Cas systems as a tool for research can 
provide an optimized platform to identify and test 
vectors for countermeasure targets. Finally, 
CRISPR-Cas antiviral therapy may provide a 
needed prophylactic treatment option for 
COVID-19 and other current and future 
pathogens. 

 

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3.1. CRISPR diagnostic platforms 
 The necessity for testing to curtail the spread 
of pandemic- and epidemic-prone diseases is of 
critical importance for adequate public health. 
When an infectious disease begins to spread, rapid 
steps must be taken to track those infected in order 
to protect those who are not. Numerous 
pandemics have emerged in the past, and in every 
instance, robust diagnostic testing to support 
pathogenic surveillance was necessary.25 In the 
early stages of confronting pandemic diseases, the 
rapid development, approval, large-scale 
manufacturing, and deployment of reliable, fast, 
and accessible diagnostic tests remains of utmost 
priority.  

Various commentators emphasized the 
importance of a robust pathogenic surveillance 
regime during the COVID-19 response: early 
detection, contact tracing, and isolation of infected 
individuals for management of contagious 
individuals to limit their transmission to others. 
Importantly, this strategy would rely heavily on 
diagnostic testing, particularly in early stages to 
prevent a major outbreak.26 In the United States, 
the average COVID-19 test sample-to-answer 
reporting time at one point during the pandemic 
was 4 days –– far beyond what is necessary for 
contact tracing –– in part because the supply chain 
did not scale up capacity for diagnostic tests and 
associated materials.27 Because COVID-19 could 
spread from individual to individual pre-
symptomatically, symptomatically, and 
asymptomatically, some studies even advocated for 
prioritizing test accessibility, frequency, and 
sample-to-answer reporting time over accuracy of 
positive results.28   

The gold standard for diagnostic testing of 
SARS-CoV-2 is the real-time reverse-
transcription polymerase chain reaction (RT-
PCR) method.29 However, this method is not 
without its many challenges. RT-PCR tests 
require specialized and expensive equipment, a 

complex molecular laboratory, and highly trained 
personnel.30 Comparatively, they are laborious and 
expensive tests.31 Moreover, they can produce false 
negative results,32 may decrease in sensitivity five 
days after onset of symptoms,33 and are susceptible 
to errors in sample collection.34 Other common 
tests such as enzyme-linked immunosorbent assays 
(ELISA) and rapid antigen and antibody tests are 
significantly cheaper in comparison to the gold 
standard RT-PCR test, but they suffer in terms of 
accuracy and exhibit particularly low sensitivity in 
the onset and first few days of illness.35  Rapid 
antigen and antibody tests are advantageous in 
accessibility for point of care and low sample-to-
answer reporting time (20-60 minutes), but suffer 
in sensitivity at 50% in comparison to RT-PCR. 36 
Furthermore, such an unprecedented demand for 
diagnostic tests amidst the COVID-19 pandemic 
led to a shortage in recommended testing supply.37  

These limiting factors for the gold standard 
RT-PCR test made it difficult to scale up 
manufacturing to a level concordant with high 
demand, often resulting in test shortages and 
prolonged sample-to-answer reporting time. 
According to the Infectious Diseases Society of 
America, test availability and a sample-to-answer 
responding time within an hour are critical 
conditions for a positive bearing on care and 
disease containment.38 In many cases, diagnostic 
strategies for adequate surveillance did not meet 
standards for the containment of COVID-19. 
Furthermore, gold standard RT-PCR tests don’t 
have the practicality to provide diagnostic testing 
to endemic regions with limited resources. 
Without specialized equipment, facilities, and 
scientists, these complex diagnostic methods 
become null. However, diagnostics remain critical 
to limit the disease spread outside of these endemic 
localities and prevent global or national outbreak.39 
Yet, countries face both global and national 
disparities in relevant resource distribution, 
including in diagnostic tests and related 

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infrastructure or intellectual property.40 The need 
for a SARS-CoV-2 test that was rapid, widely 
distributed, accessible, and accurate drove a 
dedicated effort to explore innovative diagnostic 
strategies to address the COVID-19 crisis.  
 A particularly innovative strategy was CRISPR 
diagnostics, which relies on the technology’s ability 
to locate specific segments of viral RNA. The 
approach was established in 2017, and it harnesses 
CRISPR to quickly pinpoint and tag pathogenic 
RNA without RNA isolation required by RT-
PCR tests that adds hours to the process.41,  42 
Diagnostic testing platforms used this strategy to 
deliver multiplexed and accurate detection of viral 
presence, with the reporting mechanism being 
lateral flow for an easy visual readout.43 These 
platforms are called “SHERLOCK” (specific 
high-sensitivity enzymatic reporter unlocking) and 
“DETECTR” (DNA endonuclease-targeted 
CRISPR trans reporter).43, 44 Upon development, 
the diagnostic approach was discussed as a 
revolutionary method to limit disease outbreaks of 
numerous infectious and non-infectious diseases, 
but was never approved for use.45  
 The COVID-19 pandemic reoriented 
defensive efforts within the scientific community 
towards the common objective to end the public 
health crisis, as is the case for the efforts of 
Sherlock and Mammoth Biosciences. These 
companies emphasized fast, simple, and accessible 
diagnostic capabilities, and touted the promise of 
their CRISPR platform to do so, even ceding 
bitter patent contentions for public health.46 Thus, 
Sherlock and Mammoth Biosciences adapted 
SHERLOCK and DETECTR for SARS-CoV-
2.47, 48, In March 2020, Sherlock made history with 
the first FDA authorized use of CRISPR in a 
diagnostic application, and was soon followed by 
Mammoth.49, 50 

When compared with the gold standard RT-
PCR tests, CRISPR diagnostic platforms were 
successful in offering several advantages. These 

advantages did not sacrifice accuracy. The 
SHERLOCK adaptation for SARS-CoV-2 is said 
to take an hour with results that are 100% 
concordant with the gold standard RT-PCR tests 
in terms of sensitivity and specificity.51 The 
DETECTR adaptation for SARS-CoV-2 is said 
to be an even faster sample-to-answer alternative 
to the gold standard RT-PCR tests, yet still 
comparable in terms of accuracy at 95% positive 
predictive agreement and 100% negative predictive 
agreement.48 Both SHERLOCK and DETECTR 
exhibit accessibility with ease-of-use qualities such 
as visual readouts that are converted from CRISPR 
activity.52 Furthermore, neither test requires 
complicated processing through specialized 
equipment.53 Because of this profound 
accessibility, these diagnostic platforms are also 
promising for important point-of-care testing for 
SARS-CoV-2, although they currently lack 
bureaucratic authorization outside of laboratory 
settings.48, 54  

These CRISPR diagnostic platforms continue 
to be promising with each development. Led by 
CRISPR co-inventor Jennifer Doudna, one 
research team has recently developed a CRISPR 
based diagnostic approach that can detect SARS-
CoV-2 using only a CRISPR solution and a 
mobile phone.55 The tests mix a saliva sample with 
a chemical solution that allows the CRISPR-Cas 
system to identify and cut a sequence of SARS-
CoV-2, then emit a glow strong enough for a 
smartphone to detect.56 Thus, the test is not only 
capable of reporting a positive or negative result, 
but also a quantitative estimation of the viral load 
by measuring the amount of SARS-CoV-2 
RNA.57 Advances like these aim to bring the user 
interface even closer to patients and practitioners 
to fill the gaps in diagnostic testing by making 
diagnosis user-friendly, inexpensive, and portable. 

CRISPR diagnostic platforms underscored 
notable lessons learned in how CRISPR 
technologies can be harnessed to aid current and 

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future public health responses. CRISPR 
diagnostic platforms can provide tests that are 
more accessible in terms of ease of use and cost, 
rapid in terms of sample-to-answer reporting time, 
and convenient in terms of point-of-care, all 
without sacrificing specificity or sensitivity. 
Moreover, CRISPR’s diagnostic potential to 
provide unprecedented accessibility is actively 
being discussed, including over-the-counter 
CRISPR-based tests for diseases such as COVID-
19, HPV, HIV, malaria, Zika, tuberculosis, 
dengue, and even cancer. 58, 59 CRISPR is naturally 
multiplexed, meaning that it has high potential for 
providing a test that detects multiple diseases at 
once.60 Clearly, CRISPR can support pathogenic 
surveillance regimes by providing more efficient 
avenues for identification of infected individuals, 
thereby optimizing contact tracing and disease 
management efforts.  

These factors by which CRISPR can augment 
the standards of diagnostic testing are all policy 
relevant. CRISPR diagnostic testing is rapid, 
simple, and cost-effective enough to concur with a 
timeline relevant to public health. Whereas gold 
standard RT-PCR sample-to-answer reporting 
time delays were largely due to supply chain issues 
for complicated materials and procedural issues for 
complicated processes, CRISPR tests can help 
limit pathogenic spread and optimize contact 
tracing by offering in-clinic results. It is perhaps 
equally important that detection methods 
prioritize point of care and accessibility so that 
testing strategies can feasibly extend to low- and 
lower-middle-income countries, remote 
communities that are hours away from the nearest 
health provider, and any other locality with limited 
resources or lack of required equipment. This 
accessibility factor of CRISPR is extremely policy 
relevant to prevent pathogenic spread out of 
endemic regions by both limiting the outbreak 
within these regions and reducing the need to 
travel outside of these regions. The low $1-2 cost 

per test would be feasible for consumers and 
national testing programs, expanding testing 
capacity in economic terms.61  

CRISPR-based diagnostics have not been in 
effect for long –– the first authorized use of a 
CRISPR test was in March 2020. This fact 
necessitates more studies concerning the trade-off 
between CRISPR diagnostic testing and 
alternatives like gold standard RT-PCR tests, 
particularly in terms of sensitivity and specificity. 
However, the initial application of CRISPR for 
diagnostic purposes in the COVID-19 pandemic 
is promising. The faster, more accurate, more 
accessible, easier, and cheaper diagnostic potential 
of CRISPR could improve the pathogenic 
surveillance of the COVID-19 pandemic and be a 
boon for global biopreparedness and confrontation 
of diseases. 

3.2. CRISPR assisted research 
 The necessity for rapid research on Sars-CoV-
2 facilitated by CRISPR-Cas systems enabled 
quicker development rates for public health 
countermeasures against infectious pathogens. 
CRISPR-Cas assisted screening is a process by 
which researchers can inhibit certain genetic 
functions in order to find the equivalent of a few 
needles in a haystack of a complex genome. 
Researchers often use this CRISPR “knock-out” 
technique in order to identify the effect of key 
genes. Researchers can also elicit gain of function 
by inserting a genetic sequence that the DNA 
repair mechanisms can utilize as a template when 
repairing the cuts made by the Cas proteins. These 
CRISPR “knock-in” techniques can be utilized, 
for instance, to make experimental procedures 
more applicable to a desired target.  
 During the COVID-19 pandemic, these 
research techniques were heavily utilized to better 
understand SARS-CoV-2, ultimately in order to 
develop and test disease countermeasures. 
Numerous genome-wide CRISPR screening tests 

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for SARS-CoV-2 were conducted in order to 
better understand how the virus infected human 
cells.62, 63, 64 Some of these tests sought to identify 
host factors required for SARS-CoV-2 entry with 
the intent to establish COVID-19 
countermeasures that prophylactically or 
therapeutically targeted the human cell. Other 
CRISPR screening tests sought to identify viral 
vectors with the intent to establish potential targets 
on the virus to inhibit its replication. For instance, 
researchers discovered both key host and viral 
factors that modulate SARS-CoV-2 entry into a 
human cell like the important human ACE2 
receptor or the S1/S2 boundary of the SARS-
CoV-2 spike protein.65 For the purposes of this 
report, understanding the terminology and 
complex biology behind these factors is less 
important than understanding the use of CRISPR 
in discovering them. For SARS-CoV-2 research, 
CRISPR screening techniques were notably 
utilized for the background of prophylactic and 
therapeutic treatment strategies by identifying 
factors that SARS-CoV-2 relies upon for its 
replication.  

Furthermore, researchers utilized a CRISPR 
“knock-in” technique to safely apply clinical 
evaluation to experimental trials. In one study 
conducted by Sun et al., researchers effectively 
humanized a mouse by inserting the gene for the 
host factor that allows SARS-CoV-2 to enter into 
a human cell, the ACE2 receptor.66 By eliciting a 
gain of function outcome that allowed a mouse to 
become infected by COVID-19, these researchers 
created a tool that could be used to evaluate the 
effectiveness of COVID-19 vaccines and 
therapeutic treatments in clinical trials on non-
human subjects. The mouse could then be treated 
with a vaccine, therapy, or drug that could not yet 
be ethically tried on human subjects. In the need 
for rapid development and evaluation of human-
targeted prophylactic and therapeutic 

countermeasures to a pathogen, this is a crucial 
step to optimize procedure.  

This research is the necessary background to 
continue developing and evaluating COVID-19 
therapeutic, vaccine, and drug candidates in 
clinical trials. The development of these 
countermeasures remains crucial as nations must 
continue to cope with COVID-19 cases. Beyond 
the application of COVID-19, CRISPR can be 
utilized to identify factors upon which any 
pathogen relies for replication with these 
experimental techniques. In fact, researchers are 
now identifying viral and host factors to target for 
other critical diseases –– such as HIV or malaria –
– and discussing the potential of novel 
countermeasures for these pathogens as well.67, 68 
CRISPR-Cas systems are clearly a promising 
research tool that can provide an efficient and 
accurate platform to identify and test viral vectors 
for needed antiviral therapeutic, vaccine, and drug 
targets. This tool can be utilized to optimize the 
configuration of a countermeasure against an 
emerging pathogen and mitigate its pathogenesis. 

3.3. CRISPR therapeutic treatment 
 CRISPR therapy can potentially provide an 
important countermeasure opportunity for 
COVID-19, as well as the ability to reconfigure 
treatment for other persistent and emergent 
diseases. Since December 2020, vaccines have been 
approved and rolled-out across the world in an 
effort to control the pandemic.69 However, the 
mutation rate of SARS-CoV-2 is relatively high, 
and each variant poses new challenges. Human 
behavior, motivation, and culture continue to be 
essential for effective pandemic recovery. Given 
broad societal challenges such as vaccine hesitancy 
and vaccine inequity, as well as the fact that 
vaccinated people can still be infected and spread 
COVID-19, the pandemic will persist globally.70, 

71 As the world has seen, an outbreak of COVID-
19 anywhere threatens to increase the case rate 

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everywhere. Thus, there is a persistent need for 
COVID-19 treatment options as the pandemic 
continues. This need can potentially be filled by 
CRISPR therapeutic treatment for SARS-CoV-2.  

Applying CRISPR-Cas systems as a 
countermeasure to COVID-19 has demonstrated 
promising initial evaluations, although the novel 
therapeutic option has received comparatively less 
attention than other therapeutic options.72 One 
group of Stanford-based CRISPR researchers have 
developed a CRISPR facilitated therapeutic 
approach called prophylactic antiviral CRISPR in 
human cells (PAC-MAN) that can effectively 
degrade RNA from SARS-CoV-2 in human 
cells.73 A significant challenge for the Stanford 
team is finding a delivery mechanism for the PAC-
MAN approach, most effectively targeting 
epithelial cells in the lung where the virus inflicts 
the most damage. If this barrier is overcome, the 
team believes that the PAC-MAN approach can 
be utilized as a countermeasure to all coronaviruses 
and emerging variants of SARS-CoV-2. In the 
same study, the approach was found to 
demonstrate effectiveness in degrading RNA from 
influenza in human cells.  

Another group of CRISPR researchers utilized 
a highly reprogrammable CRISPR-Cas system to 
target SARS-CoV-2 transcripts that code for 
specific proteins like the spike protein.74 As 
mentioned, the spike protein on coronaviruses was 
identified by CRISPR knock-out techniques to be 
integral for latching onto and infecting the human 
cell. Ultimately, the reprogrammable CRISPR-
Cas system demonstrated a high degree of 
effectiveness, with greater than 98% efficiency in 
silencing these regions of viral transcript. Notably, 
the group expressed concern for emerging variants 
of SARS-CoV-2 and the propensity of SARS-
CoV-2 to escape from host immunity. The 
reprogrammable nature of this CRISPR approach 
is a vital countermeasure for emerging strains of 
SARS-CoV-2, but also for the system’s 

adaptability to future emerging pathogens. Either 
the PAC-MAN approach or the reprogrammable 
CRISPR-Cas system can effectively deactivate 
SARS-CoV-2 replication cycles.  

It should be noted that CRISPR-Cas 
therapeutic treatment is subject to significant 
ethical considerations. CRISPR-Cas systems 
recently brought discussion of gene therapy back 
into the limelight after tragic setbacks related to 
other prior gene therapy techniques.75 However, 
opportunities associated with CRISPR-Cas 
systems are not without ethical concerns as well. 
This is especially true regarding CRISPR germline 
therapy that causes genetic changes at an early age 
in all cells, therefore driving through generations 
via inheritance. Somatic gene therapy through 
CRISPR, on the other hand, causes genetic 
changes in only certain cells, but still some 
commentators remain skeptical and stipulate that 
ethical distinctions between somatic editing and 
the more controversial germline editing are not as 
clear cut as they seem.76 Furthermore, due to 
research and development costs, CRISPR gene 
therapy is likely to be restrictively expensive to 
lower income individuals.77 There is also 
significant concern for limitations to CRISPR like 
off-target effects –– where the system cuts and 
replaces an unintended sequence and has 
unpredictable effects. Other limitations include 
DNA-Damage toxicity, where the editing may 
trigger effects like early cell death, or 
immunotoxicity, where the cells may build 
immunity against the therapeutic treatment.78 
These limitations are especially of concern if the 
therapeutic target is the human cell.  

CRISPR-Cas systems are known to be 
naturally occurring in bacteria with the purpose of 
deleting RNA from an infectious virus that hijacks 
cell functions. These systems can be 
therapeutically leveraged for somatic gene editing 
in human cells for the same purpose. Beyond the 
potential of these systems for this pandemic, 

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CRISPR-Cas systems can be applied to persistent 
pathogens like HIV.79 Before broad application of 
CRISPR therapies to any disease, careful ethical 
considerations and clinical trials must be carried 
out. Thus, CRISPR antiviral therapies have not 
yet been clinically applied as a countermeasure 
against COVID-19.80 Nonetheless, the pandemic 
persists and there remains great potential: 
CRISPR-Cas systems can provide a therapeutic 
treatment for SARS-CoV-2 and emerging 
variants, setting the stage for an important 
reprogrammable countermeasure for future 
pathogens. 

4. The role of CRISPR in the strategic 
environment 

 CRISPR democratizes gene editing in terms of 
ease-of-use, cost, and commercial accessibility. It 
is therefore possible for malicious non-state 
attackers to engineer a dangerous pathogen and 
cause a DBE. Some barriers to access remain for 
the attacker, including scientific knowledge in the 
field of genetics and mechanism of delivering an 
engineered pathogen. Nonetheless, the first-mover 
advantage is prominent as it is far less complicated 
to release a pathogen than to contain it. 
Unintended effects caused by a lack of scientific 
knowledge when engineering a pathogen may be 
irrelevant and still drive disease through society. 
Further, the complexity of an efficient and 
coordinated defense response with varied 
stakeholders contributes to containment 
difficulties. This comparative ease of release 
relative to containment is a key asset for the 
attacker and gives the CRISPR advantage to the 
attacker in the very short-term engineering phase 
and immediately following release.  

In the countermeasure response to a pathogen, 
efficiency and rapidity are key to containment. 
This report finds that CRISPR can be leveraged to 
rapidly configure this defense countermeasure. 
CRISPR diagnostic tests offer certain advantages 

over gold standard RT-PCR tests, including 
accessibility, sample-to-answer reporting time, 
and convenience. These tests are of critical 
importance for a pathogenic surveillance regime to 
efficiently and rapidly contain the spread. CRISPR 
tests are a key asset for the defender – especially in 
initial outbreak stages – and can be leveraged 
further to enhance the defense advantage of 
CRISPR in the short term. CRISPR offers a 
platform to identify and test viral vectors, aiding 
the configuration of countermeasures like vaccines 
and treatments. This efficient platform is to the 
advantage of the defender in the short- to mid-
term. Finally, CRISPR offers the potential 
development of therapeutic treatment options for 
the defender’s long-term countermeasure strategy 
since diseases aren’t just eradicated. CRISPR can 
also test the effectiveness of these long-term 
therapeutic treatments.  

Therefore, this report concludes that the 
decreased barrier to access for malicious actors to 
engineer a pathogen renders CRISPR more 
advantageous to a malicious, non-state actor in the 
very short-term. However, the remaining barriers 
for the attacker and the CRISPR defense 
applications against said pathogen suggest a net 
positive for the defender in the short- to mid-term 
and long-term response. The short- to mid-term 
response refers to the direct response to a biological 
event that can last months to a few years after first 
cases are identified; the long-term response refers 
to the several year- to decade-long biological 
preparation efforts from the defender. With 
increased research and development (R&D), 
applied use, and normalization of CRISPR, this 
net positive can only improve for the defender. 
Through development of policies that optimize 
CRISPR for rapid defense applications, the 
comparative advantage of CRISPR may decisively 
shift from the attacker to the defender in the very 
short-term as well. 

 

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5. Policy recommendations 

 Accordingly, this report recommends four 
policy changes: 1. R&D of CRISPR to break 
down limitations and build up social norms, 2. The 
creation of an international platform to promote 
information sharing, 3. Investment in a 
manufacturing sector for ready CRISPR 
diagnostic testing, and 4. Deployment of CRISPR 
diagnostic tests to endemic regions upon outbreak. 
These policy recommendations are not intended to 
be comprehensive. Rather the emphasis of this 
report is to identify some lessons learned from the 
applications of CRISPR during the COVID-19 
pandemic as a prompt for a rethought 
biopreparedness strategy for an evolving global 
health strategic environment. 
 CRISPR-Cas systems have several technical 
limitations that include possible off-target effects, 
immunotoxicity, and DNA-Damage toxicity. 
These limitations engender social hesitancy due to 
reasonable ethical concerns, ultimately curtailing 
the defender’s ability to configure a prepared and 
rapid public health response to a pathogen. In 
order for CRISPR to be applied to 
biopreparedness and biosafety on a needed broader 
scale, limitations and associated hesitancy must be 
addressed. Thus, the first recommendation in this 
report is increased R&D funding and efforts to 
break down limitations regarding CRISPR. 
Mounting use of the technology after limitations 
are addressed will build social norms around 
CRISPR and mitigate public hesitancy for safe 
applications.   
 One notable enabling factor for the recent 
applications of CRISPR was the decision to put 
patents aside to aid the effort to contain COVID-
19.44 This decision seems to signify that lessened 
resources devoted to court fights along with the 
information sharing for a common cause allowed 
for more efficient development and application of 
CRISPR. Scientific research builds upon other 
scientific research, and with an ever-intensifying 

threat of infectious disease, the scientific 
community must accelerate R&D of CRISPR for 
defense applications. Thus, this report also 
recommends an international platform for 
information sharing surrounding altruistic 
CRISPR research efforts for biopreparedness, 
coordinated by the World Health Organization.  
 A primary intervention for a defender 
preventing a widespread outbreak of disease is 
diagnostic testing to support an efficient 
pathogenic surveillance regime. This report 
therefore recommends incentivizing national 
private sectors to create new manufacturing 
capacity for ready CRISPR diagnostic tests for 
priority pathogens. Furthermore, this report 
recommends that nations deploy these portable 
CRISPR diagnostic tests to endemic regions upon 
outbreak. COVID-19 has demonstrated that an 
outbreak anywhere is a threat everywhere, and the 
low-cost, portable, and easy-to-use characteristics 
of CRISPR diagnostic tests could be leveraged to 
rapidly contain pathogens. 

6. Conclusion 

 The strategic environment for biosecurity is 
more unstable than ever before. CRISPR further 
exacerbates an already heightened threat of 
infectious disease by reducing barriers to entry for 
genetically engineered pathogens. At the same 
time, CRISPR is a remarkable tool for defense 
against either a natural or deliberate biological 
event. Applied use in the COVID-19 pandemic 
afforded several lessons learned for how CRISPR 
can help support pathogenic surveillance regimes, 
research, and countermeasure development. 
CRISPR must first overcome technical limitations 
and social hesitancy, then be broadly applied to 
biopreparedness strategies like CRISPR 
diagnostic tests on stand-by. This type of 
rethought approach is necessary to fully leverage 
the technology to the advantage of the defender in 
a transformed biosecurity strategic environment. 

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Before COVID-19, commentators warned of the 
emergence of a novel, pandemic-level pathogen. 
When it arrived, we were not prepared to contain 
it. Moreover, the interplay between an attacker, a 
defender, and CRISPR within the contemporary 
strategic environment does not exist in a vacuum, 
and there are also several concerning human-
driven trends that exacerbate risk: global 
warming,81-84 permafrost thaw,85,86 climate-related 
migration,87 deforestation,88,89 and loss of 
biodiversity.90 The critical need for 
biopreparedness strategies to counteract the 
increased risk of biological events, whether 
deliberate or natural, is greater than ever before. 
When the next pathogen arrives, will we have 
learned to leverage CRISPR for a prepared and 
rapid response? Our survival may depend on it. 

Acknowledgments 

 This report is produced as part of the 2021 Lisa 
J. Raines “Grand Challenge” Undergraduate 
Research Fellowship. Throughout the research 
and writing of this report I have received a great 
deal of support and assistance.  

I would first like to thank my faculty sponsor, 
Dr. Carol Kuntz, whose guidance was invaluable 
for integrating a higher degree of precision into my 
research design, overcoming research barriers, and 
writing the report for a specified audience. Our 
meetings were refreshing, clarifying, and 
ultimately brought this and future work to a higher 
level. 

I would also like to thank the  Lisa J. Raines 
Fellowship and Georgetown University’s Center 
for Research and Fellowships for affording me this 
opportunity. The program design prioritized 
interdisciplinary collaboration between a wide 
array of peer-led projects, as well as provided 
expert support and insight. This was integral to 
success in the final product of my research.  

 

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41




	Table of Contents
	Letter From the Editors
	Letter From the Editor-in-Chief Emerita
	Energy Security in Poland: Where the Energy Sector Falls Short and Where It Can Go
	Impacts of Climate Change on Mycorrhizal Fungi in Salt Marsh Habitats
	CRISPR and COVID-19: Lessons Learned to Prepare for the Next Pathogen
	The Impacts on Well-being of Undergraduate College Students Serving in a Resident Assistant Role
	About the Authors
	Acknowledgements



