Optimizing Nanoparticle Design for Gene Therapy: Protection of Oligonucleotides from Degradation Without Impeding Release of Cargo

Nanomed Nanosci Res. 2018;2(6):155. doi: 10.29011/2577-1477.100055. Epub 2018 Nov 23.

Abstract

Gene therapy delivery systems that rely on synthetic nanocarriers can be optimized by assays of nucleic acid protection and kinetic studies of nucleic acid release. These empirical measurements ensure nanoparticle stability and predict potential in vivo efficacy. Quantitative methods for assessment of the capacity of nanoparticles to protect oligonucleotide cargo and to measure the rate of release of the cargo were developed and tested based on six commercial cationic matrices. in vitro study of drug release kinetics provides predictable release rates under a variety of conditions which can be adapted to appropriate physiological factors that affect release in vivo. In brief, in vitro DNA release and DNase I degradation assays described here will be useful for optimization of nanocarrier-mediated gene therapy administration by various routes.

Keywords: Gene Therapy; Nanoparticles; Protection of Nucleic Acid Cargo; Release of Nucleic Acids from Nanoparticles.