PEO-PPO-PEO micelles as effective rAAV-mediated gene delivery systems to target human mesenchymal stem cells without altering their differentiation potency.

摘要: Abstract Recombinant adeno-associated viral (rAAV) vectors are clinically adapted gene transfer for direct human cartilage regenerative medicine. Their appropriate use in patients is still limited by a relatively low efficacy of vector penetration inside the cells, pre-existing humoral immune responses against capsid proteins large part population, and possible inhibition uptake clinical compounds such as heparin. The delivery rAAV to their targets using optimized vehicles therefore under active investigation. Here, we evaluated possibility providing bone marrow-derived mesenchymal stem cells (hMSCs), potent source via self-assembled poly(ethylene oxide) (PEO) poly(propylene (PPO) triblock copolymers linear poloxamers or X-shaped poloxamines. Encapsulation poloxamer PF68 poloxamine T908 polymeric micelles allowed an effective, durable, safe modification hMSCs levels similar even higher than those noted upon application. were capable restoring transduction with conditions inhibition, i.e. presence heparin specific antibody directed capsid, enabling effective therapeutic chondrogenic sox9 sequence leading enhanced chondrocyte differentiation cells. present findings highlight value PEO–PPO powerful tools rAAV-based Statement Significance While recombinant treat variety disorders, restricted antiviral responses, natural entry target used like search alternative routes thus becoming new field In study, describe strong benefits medicine, encapsulated based on novel, systems therapy.