A latent virus can remain in a host indefinitely, causing persistent infections. Because the viral genome is not fully eradicated by the host’s immune system, the virus may reactivate periodically. More serious ramifications of latent viral infection include the possibility of transforming the cell or forcing the cell into uncontrolled division, causing various types of cancer. While antiviral therapies can suppress active viral replication, no existing treatment can effectively eradicate latent infection. During latent infection, the dormant viral genome provides few therapeutic targets other than itself for antiviral drug development, and therefore a cure is lacking for many viral diseases of critical unmet medical need. We have developed an RNA-based CRISPR/Cas9 antiviral platform to disrupt intracellular viral DNA while leaving the host genome untouched for the treatment and elimination of persistent viral reservoirs.
Our first product is designed to disrupt human papillomavirus 16 (HPV 16) viral genome in infected cells. This product is designed for local topical application to the mucosal non-keratinized epithelium where the basal epithelial cells harbor the persistent HPV infection and is intended for patients with high-grade squamous intraepithelial lesions (HSIL), a precancerous condition where surgical excision is the current standard of care and where recurrence rates are significant.
Our HPV-CRISP/Cas9 antiviral has been well characterized using pharmacologically relevant cell models, along with rodent studies, to support in vivo target site uptake and RNA delivery. The product design was optimized to maximize the disruption of the HPV 16 genome with very high specificity (>99.9% as assessed by GUIDE-seq). We are currently advancing through preclinical development and are aiming to initiate clinical evaluation next year.
This CRISPR/Cas9 anti-HPV product will expand current HPV treatment options. By specifically targeting the HPV DNA that can hide from the immune system and from small molecule antivirals, this topical product is being designed to eliminate the viral reservoir and avoid recurrence and cancer progression. In addition to HPV, this platform is being advanced to target other persistent viral infections, including HBV, EBV and cytomegalovirus (CMV).
Wang J, Quake SR. RNA-guided endonuclease provides a therapeutic strategy to cure latent herpesviridae infection. Proc Natl Acad Sci USA. 2014;111(36):13157-62.