Breaking the bonds: non-viral vectors become chemically dynamic.
The delivery of a variety of nucleic acids such as plasmid DNA (pDNA) and small interfering RNA (siRNA) to mammalian cells is both an important research tool and potential therapeutic approach. Synthetic vehicles (SVs) that include lipoplexes and polyplexes, are widely used for non-viral delivery. A promising method of improving the efficacy of this approach is to create SVs that are chemically dynamic, so that delivery is enabled by the cleavage of chemical bonds upon exposure to various physiological environments or external stimuli. An example of this approach is the use of masked endosomolytic agents (MEAs) that improve the release of nucleic acids from endosomes, a key step during transport. When the MEA enters the acidic environment of the endosome, a pH-labile bond is broken, releasing the agent';s endosomolytic capability. Another challenge has been to develop SVs that enable in vivo delivery. Recently, an MEA that was used within dynamic polyconjugates (DPCs) enabled the efficient delivery of siRNA into hepatocytes in vivo. The use of labile bonds to mask endosomolytic agents, provides a critical design feature, because it enables efficient in vivo delivery without sacrificing endosomolytic function for release into the cytoplasm.
Wolff
Jon A
JA
Waisman Center, Department of Pediatrics and Medical Genetics, University of Wisconsin-Madison, Madison, Wisconsin, USA. jwolff@wisc.edu
Rozema
David B
DB
D000818:Animals; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000138:chemical synthesis*; D006801:Humans; D034741:RNA, Small Interfering / Q000008:administration & dosage
D034741:RNA, Small Interfering