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Capsule-like Safe Genetic Vectors—Cell-Penetrating Core–Shell Particles Selectively Release Functional Small RNA and Entrap Its Encoding DNA

Author:
Yu, Han, Pan, Houwen Matthew, Evalin,, Trau, Dieter, Patzel, Volker
Source:
ACS applied materials & interfaces 2018 v.10 no.25 pp. 21113-21124
ISSN:
1944-8252
Subject:
cell viability, encapsulation, genetic vectors, genome, humans, monocytes, particle size, recombinant DNA, small interfering RNA, tissue culture, vaccination
Abstract:
The breakthrough of genetic therapy is set back by the lack of suitable genetic vector systems. We present the development of permeability-tunable, capsule-like, polymeric, micron-sized, core–shell particles for delivery of recombinant nucleic acids into target cells. These particles were demonstrated to effectively release rod-shaped small hairpin RNA and to selectively retain the RNA-encoding DNA template, which was designed to form a bulky tripartite structure. Thus, they can serve as delivery vectors preloaded with cargo RNA or alternatively as RNA-producing micro-bioreactors. The internalization of particles by human tissue culture cells inversely correlated with particle size and with the cell to particle ratio, although at a higher than stoichiometric excess of particles over cells, cell viability was impaired. Among primary human peripheral blood mononuclear cells, up to 50% of the monocytes displayed positive uptake of particles. Finally, these particles efficiently delivered siRNA into HEK293T cells triggering functional knockdown of the target gene lamin A/C. Particle-mediated knockdown was superior to that observed after conventional siRNA delivery via lipofection. Core–shell particles protect encapsulated nucleic acids from degradation and target cell genomes from direct contact with recombinant DNA, thus representing a promising delivery vector system that can be explored for genetic therapy and vaccination.
Agid:
5982859