TY - JOUR

T1 - Random Copolymers of Lysine and Isoleucine for Efficient mRNA Delivery

AU - Pilipenko, Iuliia

AU - Korovkina, Olga

AU - Gubina, Nina

AU - Ekimova, Viktoria

AU - Ishutinova, Anastasia

AU - Korzhikova-Vlakh, Evgenia

AU - Tennikova, Tatiana

AU - Korzhikov-Vlakh, Viktor

N1 - Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/5/11

Y1 - 2022/5/11

N2 - Messenger RNA (mRNA) is currently of great interest as a new category of therapeutic agent, which could be used for prevention or treatment of various diseases. For this mRNA requires effective delivery systems that will protect it from degradation, as well as allow cellular uptake and mRNA release. Random poly(lysine-co-isoleucine) polypeptides were synthesized and investigated as possible carriers for mRNA delivery. The polypeptides obtained under lysine:isoleucine monomer ratio equal to 80/20 were shown to give polyplexes with smaller size, positive ζ-potential and more than 90% encapsulation efficacy. The phase inversion method was proposed as best way for encapsulation of mRNA into polyplexes, which are based on obtained amphiphilic copolymers. These copolymers showed efficacy in protection of bound mRNA towards ribonuclease and lower toxicity as compared to lysine homopolymer. The poly(lysine-co-isoleucine) polypeptides showed greater than poly(ethyleneimine) efficacy as vectors for transfection of cells with green fluorescent protein and firefly luciferase encoding mRNAs. This allows us to consider obtained copolymers as promising candidates for mRNA delivery applications.

AB - Messenger RNA (mRNA) is currently of great interest as a new category of therapeutic agent, which could be used for prevention or treatment of various diseases. For this mRNA requires effective delivery systems that will protect it from degradation, as well as allow cellular uptake and mRNA release. Random poly(lysine-co-isoleucine) polypeptides were synthesized and investigated as possible carriers for mRNA delivery. The polypeptides obtained under lysine:isoleucine monomer ratio equal to 80/20 were shown to give polyplexes with smaller size, positive ζ-potential and more than 90% encapsulation efficacy. The phase inversion method was proposed as best way for encapsulation of mRNA into polyplexes, which are based on obtained amphiphilic copolymers. These copolymers showed efficacy in protection of bound mRNA towards ribonuclease and lower toxicity as compared to lysine homopolymer. The poly(lysine-co-isoleucine) polypeptides showed greater than poly(ethyleneimine) efficacy as vectors for transfection of cells with green fluorescent protein and firefly luciferase encoding mRNAs. This allows us to consider obtained copolymers as promising candidates for mRNA delivery applications.

KW - cationic polypeptides

KW - mRNA delivery

KW - polyplexes

KW - random amphiphilic copolymers

KW - transfection

UR - http://www.scopus.com/inward/record.url?scp=85129718788&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/b07dd551-1e26-37d6-8160-a4b5c140fc0c/

U2 - 10.3390/ijms23105363

DO - 10.3390/ijms23105363

M3 - Article

AN - SCOPUS:85129718788

VL - 23

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 10

M1 - 5363

ER -