Innovative Approaches

A Proprietary Oligonucleotide Platform

Geron’s unique and proprietary nucleic acid chemistry platform has overcome the inherent hurdles and liabilities that have historically been associated with oligonucleotide-based drugs for human therapeutics. Certain chemical modifications have provided significantly improved binding affinity to the intended target and increased hydrolytic stability, and enabled efficient cellular uptake and biodistribution in vivo.

One of our leading oligonucleotides has a thio-phosphoramidate (NPS) backbone, which is characterized by substitution of the bridging 3’-oxygen atoms by 3’-amine groups (phosphoramidate, or NP) and the addition of sulfur atoms (thio, or S). This backbone enables enhanced binding affinity to the targeted nucleic acid in general, and the RNA template region of telomerase in particular. This molecule demonstrates high resistance to cellular nucleases, which confers stability in plasma and tissues.

A lipid palmitoyl group, covalently conjugated to the oligonucleotide via a aminoglycerol linker, improves cell permeability and biodistribution in vivo.