Unmet Need: HIV infection remains a significant global health burden despite availability of current antiviral treatments. With increasing drug resistance against available therapeutics, there is an urgent need for additional strategies to treat HIV.
Technical Details: Researchers at Johns Hopkins University have identified novel candidates for HIV prevention/treatment that can enhance host antiviral defense mechanisms to restrict HIV replication. The candidates, BCL-G and CMPK2, are previously unappreciated interferon stimulated genes (ISGs) found to be upregulated in activated CD4+ T cells from a cohort of HIV patients after treatment with type I interferon (IFN). Upregulation was also observed for known HIV restriction factors including MX2 and tetherin. In addition, induction was highly correlated with decline in circulating HIV viral RNA after treatment, indicating that upregulation of these ISG candidates can restrict HIV replication in vivo. Further validation of identified ISGs in controlling HIV was performed in vitro using siRNA knockdown of each candidate and showed loss of HIV restriction upon knockdown. Administration of exogenous BCL-G and CMPK2 would serve to enhance natural host antiviral responses as a novel treatment strategy against HIV. Overall, identified ISGs represent novel candidates for HIV treatment due to their direct restriction of HIV replication in vivo.
Value Proposition:
· Discovery of novel targets that correlate with enhanced host antiviral defense restricting HIV replication
· Unique antiviral ISGs shown to specifically restrict HIV replication in vivo
· Novel treatment strategy to enhance natural host antiviral response
· Treatment can be performed in concert with standard of care ART therapy
Looking for Partners to: Develop & commercialize the technology as a novel HIV prevention and/or treatment strategy.
Stage of Development: Pre-Clinical
Data Availability: In vivo analysis and in vitro validation of identified candidates
Inventors: David Thomas, Ashwin Balagopal, Ramy El-Diwany, Robert Siliciano, Joel Blankson, Stuar Ray, Michael Chattergoon, Justin Bailey
Publication(s): El-Diwany R, Soliman M, Sugawara S, Breitwieser F, Skaist A, Coggiano C, Sangal N, Chattergoon M, Bailey JR, Siliciano RF, Blankson JN, Ray SC, Wheelan SJ, Thomas DL, Balagopal A. (2018) CMPK2 and BCL-G are associated with type 1 interferon-induced HIV restriction in humans. Sci Adv 4(8): eaat0843.
