Communications Biology (Mar 2022)
Novel endosomolytic compounds enable highly potent delivery of antisense oligonucleotides
- Jeremy P. Bost,
- Miina Ojansivu,
- Michael J. Munson,
- Emelie Wesén,
- Audrey Gallud,
- Dhanu Gupta,
- Oskar Gustafsson,
- Osama Saher,
- Julia Rädler,
- Stuart G. Higgins,
- Taavi Lehto,
- Margaret N. Holme,
- Anders Dahlén,
- Ola Engkvist,
- Per-Erik Strömstedt,
- Shalini Andersson,
- C. I. Edvard Smith,
- Molly M. Stevens,
- Elin K. Esbjörner,
- Anna Collén,
- Samir El Andaloussi
Affiliations
- Jeremy P. Bost
- Department of Laboratory Medicine, Karolinska Institutet
- Miina Ojansivu
- Department of Medical Biochemistry and Biophysics, Karolinska Institutet
- Michael J. Munson
- Advanced Drug Delivery, Pharmaceutical Sciences, Biopharmaceutical R&D, AstraZeneca
- Emelie Wesén
- Department of Biology and Biological Engineering, Chalmers University of Technology
- Audrey Gallud
- Advanced Drug Delivery, Pharmaceutical Sciences, Biopharmaceutical R&D, AstraZeneca
- Dhanu Gupta
- Department of Laboratory Medicine, Karolinska Institutet
- Oskar Gustafsson
- Department of Laboratory Medicine, Karolinska Institutet
- Osama Saher
- Department of Laboratory Medicine, Karolinska Institutet
- Julia Rädler
- Department of Laboratory Medicine, Karolinska Institutet
- Stuart G. Higgins
- Department of Materials, Department of Bioengineering, Institute of Biomedical Engineering, Imperial College London
- Taavi Lehto
- Department of Laboratory Medicine, Karolinska Institutet
- Margaret N. Holme
- Department of Medical Biochemistry and Biophysics, Karolinska Institutet
- Anders Dahlén
- Discovery Sciences, R&D, AstraZeneca
- Ola Engkvist
- Discovery Sciences, R&D, AstraZeneca
- Per-Erik Strömstedt
- Discovery Sciences, R&D, AstraZeneca
- Shalini Andersson
- Discovery Sciences, R&D, AstraZeneca
- C. I. Edvard Smith
- Department of Laboratory Medicine, Karolinska Institutet
- Molly M. Stevens
- Department of Medical Biochemistry and Biophysics, Karolinska Institutet
- Elin K. Esbjörner
- Department of Biology and Biological Engineering, Chalmers University of Technology
- Anna Collén
- Advanced Drug Delivery, Pharmaceutical Sciences, Biopharmaceutical R&D, AstraZeneca
- Samir El Andaloussi
- Department of Laboratory Medicine, Karolinska Institutet
- DOI
- https://doi.org/10.1038/s42003-022-03132-2
- Journal volume & issue
-
Vol. 5,
no. 1
pp. 1 – 14
Abstract
Two new endosomolytic small compounds increase delivery of splice-switching oligonucleotides by interfering with their trafficking to the LAMP1-positive endosomal compartments, inducing endosomal membrane rupture and concurrent oligonucleotide escape into the cytosol.
