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1.	Bost, JP, et al. (author) Correction to "Delivery of Oligonucleotide Therapeutics: Chemical Modifications, Lipid Nanoparticles, and Extracellular Vesicles" 2021 In: ACS nano. - 1936-086X. Journal article (other academic/artistic)
2.	Bost, JP, et al. (author) Correction to "Delivery of Oligonucleotide Therapeutics: Chemical Modifications, Lipid Nanoparticles, and Extracellular Vesicles" 2021 In: ACS nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 15:11, s. 18590-18591 Journal article (other academic/artistic)
3.	Bost, Jeremy P., et al. (author) Novel endosomolytic compounds enable highly potent delivery of antisense oligonucleotides 2022 In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1 Journal article (peer-reviewed)abstract The therapeutic and research potentials of oligonucleotides (ONs) have been hampered in part by their inability to effectively escape endosomal compartments to reach their cytosolic and nuclear targets. Splice-switching ONs (SSOs) can be used with endosomolytic small molecule compounds to increase functional delivery. So far, development of these compounds has been hindered by a lack of high-resolution methods that can correlate SSO trafficking with SSO activity. Here we present in-depth characterization of two novel endosomolytic compounds by using a combination of microscopic and functional assays with high spatiotemporal resolution. This system allows the visualization of SSO trafficking, evaluation of endosomal membrane rupture, and quantitates SSO functional activity on a protein level in the presence of endosomolytic compounds. We confirm that the leakage of SSO into the cytosol occurs in parallel with the physical engorgement of LAMP1-positive late endosomes and lysosomes. We conclude that the new compounds interfere with SSO trafficking to the LAMP1-positive endosomal compartments while inducing endosomal membrane rupture and concurrent ON escape into the cytosol. The efficacy of these compounds advocates their use as novel, potent, and quick-acting transfection reagents for antisense ONs.

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Type of publication: journal article (3)

Type of content: other academic/artistic (2); peer-reviewed (1)

Author/Editor: Esbjorner, EK (3); Gupta, D. (2); Lehto, T (2); EL-Andaloussi, S (2); Holme, MN (2); Stevens, MM (2); show more...; Barriga, H (2); Gallud, A (2); Bost, JP (2); Maugeri, M (2); Valadi, H (2); Engkvist, Ola (1); Esbjörner Winters, E ... (1); Stevens, Molly M. (1); Gallud, Audrey, 1988 (1); Vilhelmsson Wesén, E ... (1); Gupta, Dhanu (1); El-Andaloussi, Samir (1); Gustafsson, Oskar (1); Dahlén, Anders (1); Holme, Margaret N. (1); Andersson, Shalini (1); Esbjörner, EK (1); Bost, Jeremy P. (1); Ojansivu, Miina (1); Munson, Michael J. (1); Saher, Osama (1); Rädler, Julia (1); Higgins, Stuart G. (1); Lehto, Taavi (1); Strömstedt, Per Erik (1); Edvard Smith, C. I. (1); Collén, Anna (1); show less...

University: Karolinska Institutet (3); Chalmers University of Technology (1)

Language: English (3)

Research subject (UKÄ/SCB): Natural sciences (1); Medical and Health Sciences (1)

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