CRISPR vs COVID-19: How can Gene Editing Help Beat the Virus

Can CRISPR help beat COVID-19? SARS- CoV-2, better known globally as coronavirus, took the world by storm after coming to rise in the city of Wuhan, China in December 2019. This pandemic shook the world and forced most nations into country-wide lockdowns. To date, this pandemic has claimed more than 12 million lives globally [1] with the death toll still rising.

Many pharmaceutical companies are struggling to find an effective therapy for COVID-stricken patients. Companies such as Pfizer have developed vaccines for the virus, but the concern is still alive as the virus regularly changes its strains. 

What is CRISPR?

CRISPR-Cas9, more commonly known as CRISPR (pronounced as crisper) is a revolutionary technique for the editing and alteration of genetic material. The alterations in the genome carried out by scientists enable them to easily manipulate the gene function, thus targeting specific aspects of any organism. The genome of any organism is the key player in controlling the cellular division and cellular function of any organism as well as the viruses containing genetic material. 

CRISPR in Bacteria: A Practical Model Against Viral Attack

CRISPR-Cas system provides a practical example of the efficacy of these systems in the adaptive immunity function of the bacteria. The primary function of this system in these microorganisms is to prevent the internal system of the bacteria from the harmful effects of foreign invaders such as bacteriophages and other mobile genetic elements. The CRISPR system in bacteria works through 3 steps:

1. Spacer Acquisition:
   The first step is spacer acquisition, which is a specific region of non-coding DNA between the genes. The spacer sequences are identified by the bacteria and integrated into the CRISPR array.
   
2. Expression:
   The spacer acquisition into the CRISPR array of the bacteria is followed by the expression of the acquired genetic material into pre-CRISPR RNA (pre-crRNA) which is transcribed by RNA polymerase. Particular endoribonucleases then cleave the resulting pre-crRNA into smaller crRNA.
   
3. Interference:
   The third and final step of the function of the CRISPR array of the bacteria is interference. This step is characterized by the recognition of the foreign genetic material of the invading agent such as a bacteriophage, which is followed by complementary base pairing of crRNA with the foreign DNA or RNA. This leads to the cleavage and destruction of the crRNA-foreign RNA/DNA complex, which leads to the elimination of foreign inclusion into the bacterium. 

CRISPR and COVID 19:

The appearance of SARS-CoV-2 in December 2019 was followed by extensive research into the pathology of the virus to develop an effective diagnostic technique as well as treatment for the disease. In this field, the abilities of CRISPR were also used. The basic reason for the existence of the CRISPR-Cas system in microorganisms such as bacteria is to eliminate the viruses that might infect the bacteria. This virus eliminating capability of CRISPR can be employed to get rid of SARS-CoV-2.

CRISPR-Based Diagnostic Tests:

Testing has proven vital in each of the COVID fighting policies enacted by various countries all over the world. Scientists have strived for finding an efficient, fast, and home-based approach for the diagnostic procedure for COVID-19 for rapid results. Due to the viral targeting abilities of CRISPR, it presents a promising approach towards developing a rapid testing system for this pathogen.

The pioneers of CRISPR techniques, Feng Zhang and Jennifer Doudna, have both launched concerted efforts towards utilizing CRISPR for diagnostic purposes for COVID-19. PCR testing for the diagnosis of COVID is indisputably a time-tested technique, but the long result times and limited supply of testing reagents have presented a major hurdle in the path of rapid testing. The SHERLOCK CRISPR testing kit for the diagnosis of COVID has been granted emergency approval by the FDA. It works by utilizing the viral targeting abilities of CRISPR. The CRISPR used in this technique is programmed towards the recognition of a specific genomic sequence of the SARS-CoV-2, which uses a specific RNA sequence to undergo complementary pairing to the SARS-CoV-2 genome. In case the target genome is found in the sample, a fluorescent marker confirms the positivity of the sample for the presence of the COVID virus. [2]

Therapeutic Strategies for COVID Utilizing CRISPR – The PAC-MAN:

The ability of CRISPR to genetically edit the viral genome promises development of many potential cures for various genetic diseases. We know that CRISPR works to protect bacteria from a phage infection, but researchers at Stanford University are working to develop a therapeutic approach towards infectious diseases using CRISPR technology. As a result, an innovative technology known as Prophylactic Antiviral CRISPR for human cells (PAC-MAN) has been developed, which has redirected the focus of the scientists to achieve the prevention of viral replication of SARS-CoV-2 by using gene-editing antiviral agents.

The PAC-MAN technology employs the working of Cas13 enzyme and specific sequences of RNA known as gRNA to target the viral genomic sequences of the coronavirus, which is the causative agent behind COVID-19. This technology prevents viral replication by targeting and destroying the viral genome sequences of the pathogen which invades the human cells. The mechanism is similar to the one used by bacteria preventing a phage infection through CRISPR. This technology proactively destroys the viral particles, thereby preventing possible infection. Moreover, this technology also shows an effective response towards all members of the Coronaviridae family which will help in the elimination of various strains and mutations of the virus. 

Synthetic peptides known as lipitoids, which have proven to be non-toxic to human cells, are also of great use in antiviral therapy. Lipitoids can deliver the CRISPR sequences effectively into the viral particles by encapsulating the sequences into nanoparticles. Once in the viral particle, these sequences then destroy the viral genome through the PAC-MAN mechanism. Therefore, combing the lipitoids with PAC-MAN technology presents a promising therapeutic strategy for COVID-19 without presenting any considerable side effects. Seeing the effective abilities of CRISPR-related diagnostic and therapeutic strategies against SARS-CoV-2, scientists believe that it will show up as an effective long-term measure against the spread of COVID. [3]

Works Cited:

1. Coronavirus Update (Live): 129,220,096 Cases and 2,821,852 Deaths from COVID-19 Virus Pandemic – Worldometer [Internet]. Worldometers.info. 2021 [cited 31 March 2021]. Available from: https://www.worldometers.info/coronavirus/?utm_campaign=homeAdvegas1?%22
2. Straiton J. CRISPR vs COVID-19: how can gene editing help beat a virus? | BioTechniques [Internet]. Future-science.com. 2021 [cited 31 March 2021]. Available from: https://www.future-science.com/doi/10.2144/btn-2020-0145
3. Abbott T, Dhamdhere G, Liu Y, Lin X, Goudy L, Zeng L et al. Development of CRISPR as an Antiviral Strategy to Combat SARS-CoV-2 and Influenza. Cell. 2020;181(4):865-876.e12.