Trecovirsen

Pedziwiatr-Werbicka E, et al. Colloids and Surfaces B: Biointerfaces, 2013, 109, 183-189.

Recent studies have highlighted the use of amino-terminated carbosilane dendrimers functionalized with quaternary ammonium (NMe3+) terminal groups as delivery vehicles for GEM91. These dendrimers exhibit water solubility and strong complexation capabilities, forming stable dendriplexes with GEM91 at optimal molar ratios. The dendriplexes demonstrate favorable physicochemical properties, including positive zeta potentials (+5 to +40 mV) and nanoscale sizes (50-600 nm), which are suitable for cellular uptake.
Stability assays have shown that GEM91-loaded dendriplexes resist degradation in the presence of serum albumin, ensuring their integrity during systemic circulation. Furthermore, cytotoxicity studies reveal that dendriplexes are significantly less harmful to erythrocytes and peripheral blood mononuclear cells (PBMCs) than unmodified dendrimers, with up to a 10-fold reduction in cytotoxicity. This biocompatibility is critical for targeting PBMCs, the main reservoirs of HIV infection.
Despite their restricted ability to deliver long-chain double-stranded nucleic acids, these dendrimers effectively transfect short-chain oligonucleotides like GEM91. This specificity underscores their utility as delivery vectors for antisense oligonucleotide therapies targeting HIV.