sifuvirtide (FS-0101) / FusoGen Pharma - LARVOL DELTA

HDAd vector-mediated in vivo HSPC engineering to express HIV fusion inhibitors imparts HIV resistance in humanized mice. (ASGCT 2026) - "Methods We generated helper-dependent adenovirus HDAd6/3 vectors expressing HIV-FIs including i) a de-immunized C46-v20, ii) a stability-enhanced C34 (Sifuvirtide, C34-SFT), and iii) the FDA- approved Enfuvirtide (T20) using various promoters (human β-actin and human ubiquitin-C for ubiquitous expression, CD68s for myeloid expression, PVT for erythroid expression)...Six weeks after humanization, HSPCs were mobilized using G-CSF and AMD3100, followed by cytokine prophylaxis and intravenous administration of an HDAd6/3 vector encoding the secreted form of C46-v20, together with HDAd6/3.SB100x vector to enable transgene integration...Conclusion The central result of this study is the demonstration that C46v20 mediates robust protection against HIV replication after in vivo HSC transduction that results in constitutive expression of the HIV-FI in humanized mice. Future studies will leverage the full cargo capacity of HDAd vectors, which can accommodate transgenes of up to..."

Preclinical • Human Immunodeficiency Virus • Infectious Disease • Targeted Protein Degradation • CD34 • CXCR4 • MGMT • MIR126 • UBC

Next-Generation Antiviral Peptides: AI-Driven Design, Translational Delivery Platforms, and Future Therapeutic Directions. (PubMed, Virus Res) - "Translational aspects are addressed by discussing novel delivery systems such as nanoparticles, hydrogels, and intranasal/inhalable formulations, as well as clinical trial examples (like, enfuvirtide (T-20), sifuvirtide, lactoferrin-based formulations, PAC-113). Finally, we explore future directions, including CRISPR- and mRNA-based peptide delivery and synergies with immune checkpoint inhibitors. By combining classical mechanisms with AI-driven design and innovative delivery platforms, this review underscores the potential of AVPs as versatile antiviral agents ready for clinical translation."

Journal • Review • Oncology

In vivo Engineering of HSPCs for HIV Gene Therapy using Helper-Dependent Adenoviral Vectors expressing HIV Fusion Inhibitors (ASGCT 2025) - "To test this, we are evaluating three fusion inhibitors expressed from two promoters (human β-Actin and human ubiquitin-C): i) de-immunized C46-v20, ii) stability-enhanced C34 (Sifuvirtide, C34-SFT), and iii) FDA-approved Enfuvirtide (T20)...To assess its safety, we performed in vivo HSPC transduction in GCSF/AMD3100-mobilized human CD46 transgenic mice...The administration of dexamethasone, MMF, and rapamycin rescued the remaining mice, suggesting inflammatory responses by/to C46-v20...We believe that this strategy will improve the safety and efficacy of HIV therapy. Disease Focus of Abstract:HIV"

Gene therapy • Preclinical • Viral vector • Gene Therapies • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Targeted Protein Degradation • CD34 • CD46 • HMGA2 • MIR126 • UBC

Refolding Dynamics of gp41 from Pre-fusion to Pre-hairpin States During HIV-1 Entry. (PubMed, J Chem Inf Model) - "Moreover, we further explored the drug-resistant mechanism of two C-terminal heptad repeat (CHR) derived gp41 inhibitors, T20 and Sifuvirtide, based on the constructed inhibitor-bound gp41 pre-hairpin complexes...Moreover, we conducted several mutant MD simulations to further investigate the mechanisms of how some drug-resistant mutations might affect the pre-hairpin formation, which in turn prevent the inhibitor recognition. Our findings provide deep structural insights into the molecular mechanisms of the pre-hairpin formation for gp41, which facilitates to guide the future anti-HIV drug design."

Journal • CXCR4