1. Artificial stem cell niche
2. Polymeric nanoparticles for liver-targeted gene delivery
Polymeric materials for liver-targeted gene delivery
The development of safe and efficient vectors or carriers for in vivo gene transfer has been one of the key challenges in fulfilling the promises of gene therapy. Viral vectors, while efficient in many gene transfer applications in vivo, pose safety concerns that are unlikely to abate in the near future, rendering synthetic carriers attractive alternatives. The synthetic vectors including cationic liposomes and polycations, while offering better safety profile, continue to suffer from low gene transfer efficiency. Mechanistic studies are essential to identify the rate-limiting steps in the non-viral gene transfer process. Controlled and systematic studies are needed in order to reveal the structure-function relationship. We have designed and synthesized a series of biodegradable polyphosphoramidate (PPA) gene carriers with the same backbone but different structural parameters (type and structure of charge group, charge density, side chain spacer, etc.) in an effort to elucidate the structure-activity relationship. The aim of this study is to investigate the structure-transfection efficiency relationship of PPA gene carriers; and to investigate the effect of PPA structure on DNA compaction ability of PPA, stability of PPA/DNA nanoparticles in physiological medium, cellular uptake efficiency, intracellular trafficking, DNA unpacking, and nuclear translocation. More importantly, the biodistribution of PPA/DNA nanoparticles and transport of nanoparticles in the liver will be correlated to the structure and gene transfer efficiency of the PPA/DNA nanoparticles.
We have prepared a PEGylated PPA to improve the stability of the PPA/DNA nanoparticles in serum containing medium. The PEG-PPA/DNA complexes formed uniform size of micelles in PBS. These micelles showed improved gene transfer efficiency in vivo.
Details in: Chua KN, Chai C, Lee PC, Tang YN, Ramakrishna S, Leong KW, Mao HQ. Surface-aminated electrospun nanofibers enhance adhesion and expansion of human umbilical cord blood hematopoietic stem/progenitor cells. Biomaterials. 27(36): 6043-6051 (2006). [PMID: 16854459]
