Journal Club: Using CRISPR to Prevent Coronavirus and Influenza Infection
· Summarized
Key takeaways
- CRISPR represents a groundbreaking approach to develop antiviral prophylactics that could potentially target multiple virus strains.
- The effectiveness of CRISPR as a treatment hinges on delivery mechanisms and overcoming challenges related to immunogenicity.
- Comparisons between traditional vaccines and CRISPR treatments highlight significant differences in how they operate, with CRISPR being more direct in suppressing viral replication.
- Future public health strategies must emphasize preparedness for pandemics, viewing CRISPR treatments as potential national defense mechanisms against viral threats.
- Antibody-dependent enhancement (ADE) presents a critical issue for vaccine development and could shift the paradigm towards CRISPR solutions.
Summary
The Promise of CRISPR in Viral Prophylaxis
The podcast discusses a novel approach harnessing CRISPR-Cas systems as a prophylactic strategy to combat viral infections, specifically targeting SARS-CoV-2 and influenza. The methodology involves using the CRISPR-Cas 13D system, which can recognize and cleave RNA viral genomes, effectively disrupting their replication process. The researchers named their system 'Pac-Man' due to its targeting abilities. The discussion delves into how this is distinct from traditional vaccines and antiviral drugs, emphasizing CRISPR’s unique potential as both prophylactic and therapeutic.
Challenges in Comparison to Traditional Vaccines and Treatments
The speakers highlight key differences in how vaccines work versus CRISPR-based treatments. Vaccines typically introduce antigens to stimulate the immune system, while CRISPR actively dismantles viral RNA. They discuss the challenges inherent in developing vaccines for complex viruses like coronaviruses and the relevance of antibody-dependent enhancement (ADE) in this context. Moreover, they explore the risk that the CRISPR approach poses less of a challenge from mutation since it employs multiple guide RNAs to target conserved regions across various viral strains.
Engineering the Future: Next Steps and Safety Considerations
Addressing the future of CRISPR in clinical settings, the speakers discuss the next steps necessary for translating this approach from lab research to practical application. They identify the importance of examining genome editing dynamics and ensuring safe delivery methods to human cells. The potential for CRISPR delivery via respiratory routes is also proposed, suggesting innovative future applications such as inhalable treatments. Despite the promise, they caution that immunogenicity and delivery are significant hurdles that need to be overcome before CRISPR can be viewed as a feasible antiviral treatment.
Business Models and the Economics of Prophylactics
The conversation turns to the economic viability of developing prophylactic treatments in comparison to traditional vaccines and antibiotics. The panel suggests that unlike antibiotics, there could be a strong commercial incentive for prophylactic approaches due to the necessity for broad distribution, especially in the face of potential pandemic threats. They emphasize a need for public investment into preparedness and the potential operational frameworks that could support rapid response to future viral outbreaks.
Reflecting on a Broader Spectrum Approach to Antivirals
Finally, the podcast contemplates the distant future where a CRISPR-based approach may pave the way for broad-spectrum antiviral treatments. The hosts speculate on the possibility of creating effective treatments against a wide range of RNA viruses, thus preventing pandemics from spreading as widely. The implications of such a transformative approach would not only redefine how we tackle viral infections but also place CRISPR at the forefront of biomedical defense strategies.
Sponsors
- NCBI · Read the article discussed in the podcast: Development of CRISPR as an Antiviral Strategy to Combat SARS-CoV-2 and Influenza
Show notes
In this episode of a16z bio Journal Club, general partner Vijay Pande, bio deal team partner Andy Tran, and bio editor Lauren Richardson discuss a novel CRISPR-Cas-based anti-viral strategy.
The discussion covers the differences between this newly developed prophylactic strategy, traditional vaccines, and anti-viral drugs; how this strategy can be engineered to target a huge range of coronavirus and influenza strains; and the next steps needed to go from paper to practice:
- “Development of CRISPR as an Antiviral Strategy to Combat SARS-CoV-2 and Influenza” in Cell (April 2020), by Timothy Abbott, Girija Dhamdhere, Yanxia Liu, Xueqiu Lin, Laine Goudy, Leiping Zeng, Augustine Chemparathy, Stephen Chmura, Nicholas Heaton, Robert Debs, Tara Pande, Drew Endy, Marie La Russa, David Lewis, and Lei Qi
a16z Journal Club (part of the a16z Podcast), curates and covers recent advances from the scientific literature -- what papers we’re reading, and why they matter from our perspective at the intersection of biology & technology (for bio journal club). You can find all these episodes at a16z.com/journalclub.
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