Incorporation of histone derived recombinant protein for enhanced disassembly of core-membrane structured liposomal nanoparticles for efficient siRNA delivery.

ABSTRACT: A novel recombinant protein tetra-H2A (TH) derived from histone H2A has been developed to replace protamine as a conditionally reversible, nucleic acid condensing agent. The novel protein will address the insufficient release of nucleic acid therapeutics, which is captured by protamine for siRNA delivery. TH is composed of 4 tandem repeats of the histone H2A N-terminal sequence, intervened by the cathepsin D cleavage site. The repeating H2A sequence enhances the binding affinity to anionic nucleic acids, forming more stable condensates, as demonstrated by the binding affinity assay. The TH/siRNA condensates are formulated into a core-membrane structured liposomal nanoparticle (NP). The endosomes of cancer cells are rich in cathepsin D, allowing on-site degradation of TH and facilitating th

SUBMITTER: Wang Y 

PROVIDER: S-EPMC5020560 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature