Rational design of peptide based siRNA transporters for enhanced intracellular siRNA delivery

Biswas, Abhijit (2021) Rational design of peptide based siRNA transporters for enhanced intracellular siRNA delivery. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (PhD thesis of Abhijit Biswas (13RS032)) 13RS032.pdf - Submitted Version Restricted to Repository staff only Download (9MB)

Abstract

siRNA is a powerful therapeutic agent which can target undruggable sites. Intracellular delivery of functional siRNA remains one of the key challenges to develop the siRNA based therapeutics. The main focus of this thesis is to develop improved peptide based molecular transporter for intracellular delivery of siRNA. In our study, we have undertaken a multiparametric approach to design the optimized siRNA binding segment and membrane permeable moiety of siRNA transporter. Chapter I summarizes the current literature of peptide based molecular transporter. This literature study helped to design advanced peptide based molecular transporter. In Chapter II, we have designed facial lipopeptide having „Arg-DHis-Arg‟ motif (AB5, AB6 and AB7) for siRNA binding sites and evaluated their efficacies. In Chapter III, we have examined the effect of lipidic moieties on molecular transporters. In Chapter IV, we have studied the effect of multivalency in siRNA transport. Different shapes and sizes of gold nanoparticle and carbon allotropes (SWCNT, MWCNT and Fullerene) conjugated with cell penetrating peptides were used to examine the effect of multivalency in siRNA delivery. Finally, we have summarized our key observations and lessons learned from the study.

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