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Enveloped viruses pseudotyped with mammalian myogenic cell fusogens target skeletal muscle for gene delivery

Entry of enveloped viruses into cells is mediated by fusogenic proteins that form a complex between membranes to drive rearrangements needed for fusion. Skeletal muscle development also requires membrane fusion events between progenitor cells to form multinucleated myofibers. Myomaker and Myomerger...

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Autores principales: Hindi, Sajedah M., Petrany, Michael J., Greenfeld, Elena, Focke, Leah C., Cramer, Alyssa A.W., Whitt, Michael A., Prasad, Vikram, Chamberlain, Jeffrey S., Podbilewicz, Benjamin, Millay, Douglas P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055243/
https://www.ncbi.nlm.nih.gov/pubmed/36993357
http://dx.doi.org/10.1101/2023.03.17.533157
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author Hindi, Sajedah M.
Petrany, Michael J.
Greenfeld, Elena
Focke, Leah C.
Cramer, Alyssa A.W.
Whitt, Michael A.
Prasad, Vikram
Chamberlain, Jeffrey S.
Podbilewicz, Benjamin
Millay, Douglas P.
author_facet Hindi, Sajedah M.
Petrany, Michael J.
Greenfeld, Elena
Focke, Leah C.
Cramer, Alyssa A.W.
Whitt, Michael A.
Prasad, Vikram
Chamberlain, Jeffrey S.
Podbilewicz, Benjamin
Millay, Douglas P.
author_sort Hindi, Sajedah M.
collection PubMed
description Entry of enveloped viruses into cells is mediated by fusogenic proteins that form a complex between membranes to drive rearrangements needed for fusion. Skeletal muscle development also requires membrane fusion events between progenitor cells to form multinucleated myofibers. Myomaker and Myomerger are muscle-specific cell fusogens, but do not structurally or functionally resemble classical viral fusogens. We asked if the muscle fusogens could functionally substitute for viral fusogens, despite their structural distinctiveness, and fuse viruses to cells. We report that engineering of Myomaker and Myomerger on the membrane of enveloped viruses leads to specific transduction of skeletal muscle. We also demonstrate that locally and systemically injected virions pseudotyped with the muscle fusogens can deliver micro-Dystrophin (μDys) to skeletal muscle of a mouse model of Duchenne muscular dystrophy. Through harnessing the intrinsic properties of myogenic membranes, we establish a platform for delivery of therapeutic material to skeletal muscle.
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spelling pubmed-100552432023-03-30 Enveloped viruses pseudotyped with mammalian myogenic cell fusogens target skeletal muscle for gene delivery Hindi, Sajedah M. Petrany, Michael J. Greenfeld, Elena Focke, Leah C. Cramer, Alyssa A.W. Whitt, Michael A. Prasad, Vikram Chamberlain, Jeffrey S. Podbilewicz, Benjamin Millay, Douglas P. bioRxiv Article Entry of enveloped viruses into cells is mediated by fusogenic proteins that form a complex between membranes to drive rearrangements needed for fusion. Skeletal muscle development also requires membrane fusion events between progenitor cells to form multinucleated myofibers. Myomaker and Myomerger are muscle-specific cell fusogens, but do not structurally or functionally resemble classical viral fusogens. We asked if the muscle fusogens could functionally substitute for viral fusogens, despite their structural distinctiveness, and fuse viruses to cells. We report that engineering of Myomaker and Myomerger on the membrane of enveloped viruses leads to specific transduction of skeletal muscle. We also demonstrate that locally and systemically injected virions pseudotyped with the muscle fusogens can deliver micro-Dystrophin (μDys) to skeletal muscle of a mouse model of Duchenne muscular dystrophy. Through harnessing the intrinsic properties of myogenic membranes, we establish a platform for delivery of therapeutic material to skeletal muscle. Cold Spring Harbor Laboratory 2023-03-18 /pmc/articles/PMC10055243/ /pubmed/36993357 http://dx.doi.org/10.1101/2023.03.17.533157 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Hindi, Sajedah M.
Petrany, Michael J.
Greenfeld, Elena
Focke, Leah C.
Cramer, Alyssa A.W.
Whitt, Michael A.
Prasad, Vikram
Chamberlain, Jeffrey S.
Podbilewicz, Benjamin
Millay, Douglas P.
Enveloped viruses pseudotyped with mammalian myogenic cell fusogens target skeletal muscle for gene delivery
title Enveloped viruses pseudotyped with mammalian myogenic cell fusogens target skeletal muscle for gene delivery
title_full Enveloped viruses pseudotyped with mammalian myogenic cell fusogens target skeletal muscle for gene delivery
title_fullStr Enveloped viruses pseudotyped with mammalian myogenic cell fusogens target skeletal muscle for gene delivery
title_full_unstemmed Enveloped viruses pseudotyped with mammalian myogenic cell fusogens target skeletal muscle for gene delivery
title_short Enveloped viruses pseudotyped with mammalian myogenic cell fusogens target skeletal muscle for gene delivery
title_sort enveloped viruses pseudotyped with mammalian myogenic cell fusogens target skeletal muscle for gene delivery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055243/
https://www.ncbi.nlm.nih.gov/pubmed/36993357
http://dx.doi.org/10.1101/2023.03.17.533157
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