Sökning: WFRF:(Lehto P) > Novel endosomolytic...
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000 | 04893naa a2200649 4500 | |
001 | oai:research.chalmers.se:324936bc-3a36-49af-83bc-1c8a6108c72f | |
003 | SwePub | |
008 | 220311s2022 | |||||||||||000 ||eng| | |
009 | oai:prod.swepub.kib.ki.se:148971700 | |
024 | 7 | a https://doi.org/10.1038/s42003-022-03132-22 DOI |
024 | 7 | a https://research.chalmers.se/publication/5290102 URI |
024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1489717002 URI |
040 | a (SwePub)cthd (SwePub)ki | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a art2 swepub-publicationtype |
072 | 7 | a ref2 swepub-contenttype |
100 | 1 | a Bost, Jeremy P.u Karolinska Institutet4 aut |
245 | 1 0 | a Novel endosomolytic compounds enable highly potent delivery of antisense oligonucleotides |
264 | c 2022-03-01 | |
264 | 1 | b Springer Science and Business Media LLC,c 2022 |
338 | a electronic2 rdacarrier | |
520 | a 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. | |
650 | 7 | a NATURVETENSKAPx Biologix Biokemi och molekylärbiologi0 (SwePub)106022 hsv//swe |
650 | 7 | a NATURAL SCIENCESx Biological Sciencesx Biochemistry and Molecular Biology0 (SwePub)106022 hsv//eng |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Läkemedelskemi0 (SwePub)301032 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medicinal Chemistry0 (SwePub)301032 hsv//eng |
650 | 7 | a NATURVETENSKAPx Kemix Organisk kemi0 (SwePub)104052 hsv//swe |
650 | 7 | a NATURAL SCIENCESx Chemical Sciencesx Organic Chemistry0 (SwePub)104052 hsv//eng |
700 | 1 | a Ojansivu, Miinau Karolinska Institutet4 aut |
700 | 1 | a Munson, Michael J.u AstraZeneca AB4 aut |
700 | 1 | a Vilhelmsson Wesén, Emelie,d 1989u Chalmers tekniska högskola,Chalmers University of Technology4 aut0 (Swepub:cth)emelin |
700 | 1 | a Gallud, Audrey,d 1988u Chalmers tekniska högskola,Chalmers University of Technology,AstraZeneca AB4 aut0 (Swepub:cth)gallud |
700 | 1 | a Gupta, Dhanuu Karolinska Institutet4 aut |
700 | 1 | a Gustafsson, Oskaru Karolinska Institutet4 aut |
700 | 1 | a Saher, Osamau Karolinska Institutet4 aut |
700 | 1 | a Rädler, Juliau Karolinska Institutet4 aut |
700 | 1 | a Higgins, Stuart G.u Imperial College of Science, Technology and Medicine4 aut |
700 | 1 | a Lehto, Taaviu Karolinska Institutet4 aut |
700 | 1 | a Holme, Margaret N.u Karolinska Institutet4 aut |
700 | 1 | a Dahlén, Andersu AstraZeneca AB4 aut |
700 | 1 | a Engkvist, Olau AstraZeneca AB4 aut |
700 | 1 | a Strömstedt, Per Eriku AstraZeneca AB4 aut |
700 | 1 | a Andersson, Shaliniu AstraZeneca AB4 aut |
700 | 1 | a Edvard Smith, C. I.u Karolinska Institutet4 aut |
700 | 1 | a Stevens, Molly M.u Karolinska Institutet4 aut |
700 | 1 | a Esbjörner Winters, Elin,d 1978u Chalmers tekniska högskola,Chalmers University of Technology4 aut0 (Swepub:cth)eline |
700 | 1 | a Collén, Annau AstraZeneca AB4 aut |
700 | 1 | a El-Andaloussi, Samiru Karolinska Institutet4 aut |
700 | 1 | a Esbjorner, EK4 aut |
710 | 2 | a Karolinska Institutetb AstraZeneca AB4 org |
773 | 0 | t Communications Biologyd : Springer Science and Business Media LLCg 5:1q 5:1x 2399-3642 |
856 | 4 | u https://research.chalmers.se/publication/529010/file/529010_Fulltext.pdfx primaryx freey FULLTEXT |
856 | 4 | u https://www.nature.com/articles/s42003-022-03132-2.pdf |
856 | 4 8 | u https://doi.org/10.1038/s42003-022-03132-2 |
856 | 4 8 | u https://research.chalmers.se/publication/529010 |
856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:148971700 |
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