Novel cell-penetrating peptide-adaptors effect intracellular delivery and endosomal escape of protein cargos
The use of cell-penetrating peptides (CPPs) as biomolecular delivery vehicles holds great promise for therapeutic and other applications, but development has been stymied by poor delivery and lack of endosomal escape. We have developed a CPP-adaptor system capable of efficient intracellular delivery...
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Veröffentlicht in: | Journal of cell science 2016-03, Vol.129 (5), p.893-897 |
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creator | Salerno, John C Ngwa, Verra M Nowak, Scott J Chrestensen, Carol A Healey, Allison N McMurry, Jonathan L |
description | The use of cell-penetrating peptides (CPPs) as biomolecular delivery vehicles holds great promise for therapeutic and other applications, but development has been stymied by poor delivery and lack of endosomal escape. We have developed a CPP-adaptor system capable of efficient intracellular delivery and endosomal escape of user-defined protein cargos. The cell-penetrating sequence of HIV transactivator of transcription was fused to calmodulin, which binds with subnanomolar affinity to proteins containing a calmodulin binding site. Our strategy has tremendous advantage over prior CPP technologies because it utilizes high-affinity non-covalent, but reversible coupling between CPP and cargo. Three different cargo proteins fused to a calmodulin binding sequence were delivered to the cytoplasm of eukaryotic cells and released, demonstrating the feasibility of numerous applications in living cells including alteration of signaling pathways and gene expression. |
doi_str_mv | 10.1242/jcs.182113 |
format | Article |
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We have developed a CPP-adaptor system capable of efficient intracellular delivery and endosomal escape of user-defined protein cargos. The cell-penetrating sequence of HIV transactivator of transcription was fused to calmodulin, which binds with subnanomolar affinity to proteins containing a calmodulin binding site. Our strategy has tremendous advantage over prior CPP technologies because it utilizes high-affinity non-covalent, but reversible coupling between CPP and cargo. Three different cargo proteins fused to a calmodulin binding sequence were delivered to the cytoplasm of eukaryotic cells and released, demonstrating the feasibility of numerous applications in living cells including alteration of signaling pathways and gene expression.</description><identifier>ISSN: 0021-9533</identifier><identifier>EISSN: 1477-9137</identifier><identifier>DOI: 10.1242/jcs.182113</identifier><identifier>PMID: 26801086</identifier><language>eng</language><publisher>England: The Company of Biologists Ltd</publisher><subject>Calmodulin - chemistry ; Cell-Penetrating Peptides - chemistry ; Cell-Penetrating Peptides - metabolism ; Endosomes - metabolism ; Gene Products, tat - chemistry ; HEK293 Cells ; Humans ; Myoglobin - metabolism ; Protein Transport ; Recombinant Fusion Proteins - chemistry ; Recombinant Fusion Proteins - metabolism ; Short Report</subject><ispartof>Journal of cell science, 2016-03, Vol.129 (5), p.893-897</ispartof><rights>2016. 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Three different cargo proteins fused to a calmodulin binding sequence were delivered to the cytoplasm of eukaryotic cells and released, demonstrating the feasibility of numerous applications in living cells including alteration of signaling pathways and gene expression.</description><subject>Calmodulin - chemistry</subject><subject>Cell-Penetrating Peptides - chemistry</subject><subject>Cell-Penetrating Peptides - metabolism</subject><subject>Endosomes - metabolism</subject><subject>Gene Products, tat - chemistry</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Myoglobin - metabolism</subject><subject>Protein Transport</subject><subject>Recombinant Fusion Proteins - chemistry</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Short Report</subject><issn>0021-9533</issn><issn>1477-9137</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkcFKJDEQhoMoOqte9gGWHEVoTSXpTvoiLKK7guhFzyFJV4-RTKdNegZ8e3sYV9ZTHerjr7_4CPkJ7AK45JevvlyA5gBijyxAKlW1INQ-WTDGoWprIY7Ij1JeGWOKt-qQHPFGM2C6WZD4kDYYqccYqxEHnLKdwrCkI45T6LCynR2nlAvFvkc_0TDMxJZeR5tphzFsML9TO3QUhy6VtLKRYvF2RJp6OuY0YRiot3mZygk56G0sePo5j8nz7c3T9d_q_vHP3fXv-8oLpaeqVhKU8LZvG6mYc047K1yrWa00SgGydgIaJx2Tvahrp1XdM-Ya0dimBbTimFztcse1W2HncVs6mjGHlc3vJtlgvm-G8GKWaWOkBiE4zAFnnwE5va2xTGYVyvZrO2BaFwNKMc55w9oZPd-hPqdSMvZfZ4CZrR4z6zE7PTP86_9iX-g_H-IDeDGNuQ</recordid><startdate>20160301</startdate><enddate>20160301</enddate><creator>Salerno, John C</creator><creator>Ngwa, Verra M</creator><creator>Nowak, Scott J</creator><creator>Chrestensen, Carol A</creator><creator>Healey, Allison N</creator><creator>McMurry, Jonathan L</creator><general>The Company of Biologists Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160301</creationdate><title>Novel cell-penetrating peptide-adaptors effect intracellular delivery and endosomal escape of protein cargos</title><author>Salerno, John C ; Ngwa, Verra M ; Nowak, Scott J ; Chrestensen, Carol A ; Healey, Allison N ; McMurry, Jonathan L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-574173caf96470bbb8ba3b980578e43145b316b4b04f355b875f00b636a691ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Calmodulin - chemistry</topic><topic>Cell-Penetrating Peptides - chemistry</topic><topic>Cell-Penetrating Peptides - metabolism</topic><topic>Endosomes - metabolism</topic><topic>Gene Products, tat - chemistry</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Myoglobin - metabolism</topic><topic>Protein Transport</topic><topic>Recombinant Fusion Proteins - chemistry</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Short Report</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Salerno, John C</creatorcontrib><creatorcontrib>Ngwa, Verra M</creatorcontrib><creatorcontrib>Nowak, Scott J</creatorcontrib><creatorcontrib>Chrestensen, Carol A</creatorcontrib><creatorcontrib>Healey, Allison N</creatorcontrib><creatorcontrib>McMurry, Jonathan L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cell science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Salerno, John C</au><au>Ngwa, Verra M</au><au>Nowak, Scott J</au><au>Chrestensen, Carol A</au><au>Healey, Allison N</au><au>McMurry, Jonathan L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel cell-penetrating peptide-adaptors effect intracellular delivery and endosomal escape of protein cargos</atitle><jtitle>Journal of cell science</jtitle><addtitle>J Cell Sci</addtitle><date>2016-03-01</date><risdate>2016</risdate><volume>129</volume><issue>5</issue><spage>893</spage><epage>897</epage><pages>893-897</pages><issn>0021-9533</issn><eissn>1477-9137</eissn><abstract>The use of cell-penetrating peptides (CPPs) as biomolecular delivery vehicles holds great promise for therapeutic and other applications, but development has been stymied by poor delivery and lack of endosomal escape. 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source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection; Company of Biologists |
subjects | Calmodulin - chemistry Cell-Penetrating Peptides - chemistry Cell-Penetrating Peptides - metabolism Endosomes - metabolism Gene Products, tat - chemistry HEK293 Cells Humans Myoglobin - metabolism Protein Transport Recombinant Fusion Proteins - chemistry Recombinant Fusion Proteins - metabolism Short Report |
title | Novel cell-penetrating peptide-adaptors effect intracellular delivery and endosomal escape of protein cargos |
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