Internal Reference:听2024-103

Market Need听

Human immunodeficiency virus type 1 (HIV-1) infection is currently managed with combination antiretroviral therapy (cART), which effectively delays progression to acquired immunodeficiency syndrome (AIDS). However, cART is not curative and requires lifelong adherence, placing a financial burden on patients and healthcare systems and posing risks of long-term side effects. Gene therapy offers a promising alternative, aiming for a functional cure by eliminating the need for continuous treatment. Several antiviral RNA strategies鈥攕uch as short hairpin RNAs (shRNAs), aptamers, ribozymes, and U1 interference RNAs鈥攈ave been developed to inhibit HIV replication. Like cART, combination approaches are essential to prevent resistance, and multiple anti-HIV RNA therapies have reached clinical evaluation. Among these, shRNAs targeting conserved regions of the HIV genome remain leading candidates. The university has screened a wide range of shRNAs and identified six novel constructs that are unique combinations of promoter, short hairpin RNA (shRNA), and aptamer conjugates that demonstrate superior anti-HIV efficacy and an excellent safety profile, achieving strong viral inhibition with no adverse effects on cell proliferation.

Technology Overview

This technology uses shRNA-aptamer conjugates to effectively inhibit HIV replication, offering a novel strategy toward a functional cure through combination RNA-based gene therapy. Six optimized gene constructs have been identified, combining different promoters, shRNAs, and aptamer conjugates that achieve superior HIV inhibition without affecting cell proliferation. These constructs outperform previous shRNA candidates in clinical development and represent strong candidates for future combinatorial therapies to overcome viral resistance and advance HIV cure strategies.

Commercial Advantages

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• Superior Efficacy and Safety: The selected shRNA-aptamer chimeras outperform two clinical-stage candidates by achieving strong inhibition of HIV replication, with no cytotoxicity or other adverse effects.
• Resistance Prevention: By combining multiple shRNAs that target distinct conserved regions of the HIV genome, similar to the cART strategy, the approach offers a more durable and resistance-avoiding gene therapy.
• Best-in-Class potential: While other gene therapy strategies, including CCR5 knockout and various anti-HIV RNAs, have entered clinical trials, none have demonstrated a comparable balance of potency and safety.

Additional Information

• Researcher: Anne Gatignol
• Patents:听United States听Provisional听(Filed)
• Funding: Commercialization Priming
• Keywords: Infectious Diseases, Gene Therapy