Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Design of the Oligonucleotide Carriers: Importance of Polyamine Chain Length

Version 1 : Received: 22 October 2018 / Approved: 23 October 2018 / Online: 23 October 2018 (04:16:11 CEST)

A peer-reviewed article of this Preprint also exists.

Annenkov, V.V.; Krishnan, U.M.; Pal’shin, V.A.; Zelinskiy, S.N.; Kandasamy, G.; Danilovtseva, E.N. Design of Oligonucleotide Carriers: Importance of Polyamine Chain Length. Polymers 2018, 10, 1297. Annenkov, V.V.; Krishnan, U.M.; Pal’shin, V.A.; Zelinskiy, S.N.; Kandasamy, G.; Danilovtseva, E.N. Design of Oligonucleotide Carriers: Importance of Polyamine Chain Length. Polymers 2018, 10, 1297.

Abstract

Amine containing polymers are extensively studied as special carriers for short-chain RNA (13–25 nucleotides) which are applied as gene silencing agent in gene therapy of various diseases including cancer. Elaboration of the oligonucleotide carriers requires knowledge about peculiarities of oligonucleotide - polymeric amine interaction. Critical length of the interacting chains is the important parameter which allows to design sophisticated constructions containing oligonucleotide binding segments, solubilizing, protective and aiming parts. We studied interaction of (TCAG)n, n=1-6 DNA oligonucleotides with polyethylenimine and poly(N-(3-((3-(dimethyl­amino)propyl)(methyl)amino)propyl)-N-methylacrylamide). Critical length for oligonucleotides in interaction with polymeric amines is 8-12 units and complexation at these length can be accompanied by "all-or-nothing" effects. New dimethylacrylamide based polymers with grafted polyamine chains were obtained and studied in complexation with DNA and RNA oligonucleotides. The most effective interaction and transfection activity into A549 cancer cells was found for a sample with average number of nitrogens in polyamine chain equal to 27, i.e. for a sample in which all grafted chains are longer the critical length for polymeric amine - oligonucleotide complexation.

Keywords

polymeric amines; oligonucleotides; critical length; grafted polyamines; gene delivery

Subject

Chemistry and Materials Science, Polymers and Plastics

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