Glycosylated RAFT polymers with varying PEG linkers produce different siRNA uptake, gene silencing and toxicity profiles.

Glycosylated RAFT polymers with varying PEG linkers produce different siRNA uptake, gene silencing and toxicity profiles. Biomacromolecules. 2017 Oct 23;: Authors: Williams EGL, Hutt OE, Hinton TM, Larnaudie SC, Le T, MacDonald JM, Gunatillake P, Thang SH, Duggan PJ Abstract Achieving efficient and targeted delivery of short interfering (siRNA) is an important research challenge to overcome to render highly promising siRNA therapies clinically successful. Challenges exist in designing synthetic carriers for these RNAi constructs that provide protection against serum degradation, extended blood retention times, effective cellular uptake through a variety of uptake mechanisms, endosomal escape and efficient cargo release. These challenges have resulted in a significant body of research, and led to many important findings about the chemical composition and structural layout of the delivery vector for optimal gene silencing. The challenge of targeted delivery vectors remains, and strategies to take advantage of nature's self-selective cellular uptake mechanisms for specific organ cells, such as the liver, have enabled researchers to step closer to achieving this goal. In this work we report the design, synthesis and biological evaluation of a novel polymeric delivery vector, incorporating galactose moieties to target hepatic cells through clathrin-mediated endocytosis at asialoglycoprotein receptors. An investigation into the density of ...
Source: Biomacromolecules - Category: Biochemistry Authors: Tags: Biomacromolecules Source Type: research