A modified CD9 tag for efficient protein delivery via extracellular vesicles
Extracellular vesicles (EVs) are attracting growing attention for therapeutic use and as diagnostic markers, particularly for cancer. Although therapies based on small interfering RNAs are under intensive research, other therapeutic molecules, especially proteins, have not been sufficiently investig...
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| Veröffentlicht in: | PloS one 2024-10, Vol.19 (10), p.e0310083 |
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| description | Extracellular vesicles (EVs) are attracting growing attention for therapeutic use and as diagnostic markers, particularly for cancer. Although therapies based on small interfering RNAs are under intensive research, other therapeutic molecules, especially proteins, have not been sufficiently investigated. One of the major method for loading proteins into EVs is electroporation; however, it damages membrane integrity and requires repeated purification, precluding clinical applications. Thus, natural and efficient protein transfer is a prerequisite for the clinical application of protein-based EV therapy. Another prerequisite is an efficient endosomal escape, as most EVs incorporated into receptor cells result in endosomal degradation. Therefore, we generated a short CD9 (sCD9)-INF/TAT tag for efficiently transfers fused proteins to the EV and enhances endosomal escape to address the abovementioned problems. Interestingly, protein transfer via EVs drastically improved when the EV producer and receptor cells were cocultured, strongly indicating bystander effects of cells producing therapeutic proteins fused with a sCD9-INF/TAT tag. This method can be applied to a wide range of therapeutic technologies, including cellular transplantation or viral therapy. |
| doi_str_mv | 10.1371/journal.pone.0310083 |
| format | Article |
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Although therapies based on small interfering RNAs are under intensive research, other therapeutic molecules, especially proteins, have not been sufficiently investigated. One of the major method for loading proteins into EVs is electroporation; however, it damages membrane integrity and requires repeated purification, precluding clinical applications. Thus, natural and efficient protein transfer is a prerequisite for the clinical application of protein-based EV therapy. Another prerequisite is an efficient endosomal escape, as most EVs incorporated into receptor cells result in endosomal degradation. Therefore, we generated a short CD9 (sCD9)-INF/TAT tag for efficiently transfers fused proteins to the EV and enhances endosomal escape to address the abovementioned problems. Interestingly, protein transfer via EVs drastically improved when the EV producer and receptor cells were cocultured, strongly indicating bystander effects of cells producing therapeutic proteins fused with a sCD9-INF/TAT tag. This method can be applied to a wide range of therapeutic technologies, including cellular transplantation or viral therapy.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0310083</identifier><identifier>PMID: 39418272</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Antibodies ; Biology and Life Sciences ; CD9 antigen ; Chromatography ; Dosage and administration ; Electroporation ; Endosomes - metabolism ; Extracellular vesicles ; Extracellular Vesicles - metabolism ; Health aspects ; HEK293 Cells ; Humans ; Lipid membranes ; Physiological aspects ; Plasmids ; Protein purification ; Protein therapy ; Protein Transport ; Proteins ; Receptors ; Recombinant Fusion Proteins - genetics ; Recombinant Fusion Proteins - metabolism ; Research and Analysis Methods ; Tat protein ; Tetraspanin 29 - metabolism ; Therapeutic applications ; Vesicles</subject><ispartof>PloS one, 2024-10, Vol.19 (10), p.e0310083</ispartof><rights>Copyright: © 2024 Inano, Kitano. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2024 Public Library of Science</rights><rights>2024 Inano, Kitano. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 Inano, Kitano 2024 Inano, Kitano</rights><rights>2024 Inano, Kitano. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Interestingly, protein transfer via EVs drastically improved when the EV producer and receptor cells were cocultured, strongly indicating bystander effects of cells producing therapeutic proteins fused with a sCD9-INF/TAT tag. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Inano, Shojiro</au><au>Kitano, Toshiyuki</au><au>Kim, Cheorl-Ho</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A modified CD9 tag for efficient protein delivery via extracellular vesicles</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2024-10-17</date><risdate>2024</risdate><volume>19</volume><issue>10</issue><spage>e0310083</spage><pages>e0310083-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Extracellular vesicles (EVs) are attracting growing attention for therapeutic use and as diagnostic markers, particularly for cancer. Although therapies based on small interfering RNAs are under intensive research, other therapeutic molecules, especially proteins, have not been sufficiently investigated. One of the major method for loading proteins into EVs is electroporation; however, it damages membrane integrity and requires repeated purification, precluding clinical applications. Thus, natural and efficient protein transfer is a prerequisite for the clinical application of protein-based EV therapy. Another prerequisite is an efficient endosomal escape, as most EVs incorporated into receptor cells result in endosomal degradation. Therefore, we generated a short CD9 (sCD9)-INF/TAT tag for efficiently transfers fused proteins to the EV and enhances endosomal escape to address the abovementioned problems. Interestingly, protein transfer via EVs drastically improved when the EV producer and receptor cells were cocultured, strongly indicating bystander effects of cells producing therapeutic proteins fused with a sCD9-INF/TAT tag. This method can be applied to a wide range of therapeutic technologies, including cellular transplantation or viral therapy.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>39418272</pmid><doi>10.1371/journal.pone.0310083</doi><orcidid>https://orcid.org/0000-0003-0210-1158</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Antibodies Biology and Life Sciences CD9 antigen Chromatography Dosage and administration Electroporation Endosomes - metabolism Extracellular vesicles Extracellular Vesicles - metabolism Health aspects HEK293 Cells Humans Lipid membranes Physiological aspects Plasmids Protein purification Protein therapy Protein Transport Proteins Receptors Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism Research and Analysis Methods Tat protein Tetraspanin 29 - metabolism Therapeutic applications Vesicles |
| title | A modified CD9 tag for efficient protein delivery via extracellular vesicles |
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