Byungji Kim1, Ji-Ho Park2, Michael J Sailor1,3. 1. Materials Science and Engineering Program, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA. 2. Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea. 3. Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA.
Abstract
With the recent FDA approval of the first siRNA-derived therapeutic, RNA interference (RNAi)-mediated gene therapy is undergoing a transition from research to the clinical space. The primary obstacle to realization of RNAi therapy has been the delivery of oligonucleotide payloads. Therefore, the main aims is to identify and describe key design features needed for nanoscale vehicles to achieve effective delivery of siRNA-mediated gene silencing agents in vivo. The problem is broken into three elements: 1) protection of siRNA from degradation and clearance; 2) selective homing to target cell types; and 3) cytoplasmic release of the siRNA payload by escaping or bypassing endocytic uptake. The in vitro and in vivo gene silencing efficiency values that have been reported in publications over the past decade are quantitatively summarized by material type (lipid, polymer, metal, mesoporous silica, and porous silicon), and the overall trends in research publication and in clinical translation are discussed to reflect on the direction of the RNAi therapeutics field.
With the recent FDA approval of the first siRNA-derived therapeutic, RNA interference (RNAi)-mediated gene therapy is undergoing a transition from research to the clinical space. The primary obstacle to realization of RNAi therapy has been the delivery of n class="Chemical">oligonucleotide payloads. Therefore, the main aims is to identify anpan>d describe key designpan> features needed for nanpan>oscale vehicles to achieve effective delivery of siRNA-mediated gene silencing agents in vivo. The problem is broken into three elements: 1) protectionpan> of siRNA from degradationpan> anpan>d clearanpan>ce; 2) selective homing to target cell types; anpan>d 3) cytoplasmic release of the siRNA payload by escaping or bypassing endocytic uptake. The in vitro anpan>d in vivo gene silencing efficiency values that have been reported in publicationpan>s over the past decade are quanpan>titatively summarized by material type (pan> class="Chemical">lipid, polymer, metal, mesoporous silica, and porous silicon), and the overall trends in research publication and in clinical translation are discussed to reflect on the direction of the RNAi therapeutics field.
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