Caprin-1 Promotes Cellular Uptake of Nucleic Acids with Backbone and Sequence Discrimination

被引：8

作者：

Galli, Valentina ^{[1
,2
]}

Sadhu, Kalyan K. ^{[1
,2
]}

Masi, Daniela ^{[1
,2
]}

Saarbach, Jacques ^{[1
,2
]}

Roux, Aurelien ^{[1
,2
]}

Winssinger, Nicolas ^{[1
,2
]}

机构：

[1] Univ Geneva, Fac Sci, Sch Chem & Biochem, CH-1211 Geneva, Switzerland

[2] Univ Geneva, Natl Ctr Competence Res NCCR Chem Biol, CH-1211 Geneva, Switzerland

来源：

HELVETICA CHIMICA ACTA | 2020年 / 103卷 / 01期

基金：

瑞士国家科学基金会; 欧洲研究理事会;

关键词：

peptide nucleic acids; cellular uptake; caprin-1; antisense agents; ENCODED SYNTHESIS PES; PNA SYNTHESIS; TUMOR-GROWTH; PEPTIDE; DNA; PROTEIN; OLIGONUCLEOTIDES; IDENTIFICATION; METASTASIS; LIBRARIES;

D O I：

10.1002/hlca.201900255

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The cellular delivery of oligonucleotides has been a major obstacle in the development of therapeutic antisense agents. PNAs (Peptide Nucleic Acid) are unique in providing a modular peptidic backbone that is amenable to structural and charge modulation. While cationic PNAs have been shown to be taken up by cells more efficiently than neutral PNAs, the generality of uptake across different nucleobase sequences has never been tested. Herein, we quantified the relative uptake of PNAs across a library of 10 000 sequences for two different PNA backbones (cationic and neutral) and identified sequences with high uptake and low uptake. We used the high uptake sequence as a bait for target identification, leading to the discovery that a protein, caprin-1, binds to PNA with backbone and sequence discrimination. We further showed that purified caprin-1 added to cell cultures enhanced the cellular uptake of PNA as well as DNA and RNA.

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页数：10

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