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- Title
Caprin‐1 Promotes Cellular Uptake of Nucleic Acids with Backbone and Sequence Discrimination.
- Authors
Galli, Valentina; Sadhu, Kalyan K.; Masi, Daniela; Saarbach, Jacques; Roux, Aurélien; Winssinger, Nicolas
- Abstract
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.
- Subjects
NUCLEIC acids; PEPTIDE nucleic acids; OLIGONUCLEOTIDES; SPINE; CELL culture
- Publication
Helvetica Chimica Acta, 2020, Vol 103, Issue 1, pN.PAG
- ISSN
0018-019X
- Publication type
Article
- DOI
10.1002/hlca.201900255