Surface-shielded polycationic vectors for nucleic acid delivery

Eliška Hrdá
Lecture of the lecture cycle
16.12.2024 10:00, Lecture room A

To achieve successful gene therapy, various vectors for nucleic acid (NA) delivery are being developed. This study focuses on the design and synthesis of polycationic vectors based on di-block copolymers consisting of a methacrylate-type cationic block and an electroneutral hydrophilic block. The cationic vector blocks, containing permanently charged trimethylammonium (TMA) or tributylphosphonium (TBP) groups and 0-20 mol% hydrophobic butyl groups, are able to efficiently complex DNA to form 100-200 nm nanoparticles. The hydrophilic blocks based on 2-methacryloyloxyethylphosphorylcholine (MPC) or N-(2-hydroxypropyl) methacrylamide (HPMA) coat the nanoparticle surfaces with an electroneutral polymer layer. In addition, pH-responsive hydrazone bonds are incorporated between the TMA and TBP groups and the polymer backbone of the polycationic block to enable pH-sensitive NA release. This model study provides insight into the process of NA complexation/decomplexation by pH-responsive di-block polycationic vectors. Theoretically, the vectors facilitate DNA release from the complex in a mildly acidic environment within cells while maintaining its stability under neutral blood conditions, with in vitro experiments currently underway.

The lecture is presented in English