Self-delivering RNAi compounds as therapeutic agents in the central nervous system to enhance axonal regeneration after injury.

ABSTRACT: The therapeutic use of RNAi has grown but often faces several hurdles related to delivery systems, compound stability, immune activation, and on-target/off-tissue effects. Self-delivering RNAi (sdRNA) molecules do not require delivery agents or excipients. Here we demonstrate the ability of sdRNA to reduce the expression of PTEN (phosphatase and tensin homolog) to stimulate regenerative axon regrowth in the injured adult CNS. PTEN-targeting sdRNA compounds were tested for efficacy in vivo by intravitreal injection after adult rat optic nerve injury. We describe critical steps in lead compound generation through the optimization of nucleotide modifications, enhancements for stability in biological matrices, and screening for off-target immunostimulatory activity. The data show that P

SUBMITTER: Woller SA 

PROVIDER: S-EPMC9127586 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature