Charge-altering releasable transporters (CARTs) for the delivery and release of mRNA in living animals
Functional delivery of mRNA to tissues in the body is key to implementing fundamentally new and potentially transformative strategies for vaccination, protein replacement therapy, and genome editing, collectively affecting approaches for the prevention, detection, and treatment of disease. Broadly a...
Gespeichert in:
| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2017-01, Vol.114 (4), p.E448-E456 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | E456 |
|---|---|
| container_issue | 4 |
| container_start_page | E448 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 114 |
| creator | McKinlay, Colin J. Vargas, Jessica R. Blake, Timothy R. Hardy, Jonathan W. Kanada, Masamitsu Contag, Christopher H. Wender, Paul A. Waymouth, Robert M. |
| description | Functional delivery of mRNA to tissues in the body is key to implementing fundamentally new and potentially transformative strategies for vaccination, protein replacement therapy, and genome editing, collectively affecting approaches for the prevention, detection, and treatment of disease. Broadly applicable tools for the efficient delivery of mRNA into cultured cells would advance many areas of research, and effective and safe in vivo mRNA delivery could fundamentally transform clinical practice. Here we report the step-economical synthesis and evaluation of a tunable and effective class of synthetic biodegradable materials: charge-altering releasable transporters (CARTs) for mRNA delivery into cells. CARTs are structurally unique and operate through an unprecedented mechanism, serving initially as oligo(α-amino ester) cations that complex, protect, and deliver mRNA and then change physical properties through a degradative, charge-neutralizing intramolecular rearrangement, leading to intracellular release of functional mRNA and highly efficient protein translation. With demonstrated utility in both cultured cells and animals, this mRNA delivery technology should be broadly applicable to numerous research and therapeutic applications. |
| doi_str_mv | 10.1073/pnas.1614193114 |
| format | Article |
| fullrecord | <record><control><sourceid>jstor_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5278438</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>26479058</jstor_id><sourcerecordid>26479058</sourcerecordid><originalsourceid>FETCH-LOGICAL-c536t-2b9a929bb2d427c0b5088896a674f8177e309754b70a172fffb80b54b310a1613</originalsourceid><addsrcrecordid>eNpdkctrGzEQxkVpaNy0555aRHtJD5votXpcCsb0EQgphPQstPLIXrOWXGkdyH9fLXaTNqcBfb_5NDMfQu8ouaBE8ctddOWCSiqo4ZSKF2hGiaGNFIa8RDNCmGq0YOIUvS5lQwgxrSav0CnTRBoj2hkKi7XLK2jcMELu4wpnGMAV1w2Ax-xi2aVclYLPF_Pbu_IZh5TxuAa8hKG_h_yAXVwemwCngLe3N3PcR1zVyc7FfuuG8gadhFrg7bGeoV_fvt4tfjTXP79fLebXjW-5HBvWGWeY6Tq2FEx50rVEa22kk0oETZUCToxqRaeIo4qFEDpdIdFxWh8k5Wfoy8F3t--2sPQQ6xKD3eU6RX6wyfX2fyX2a7tK97ZlSguuq8HHg0EqY2-L70fwa59iBD9ayrmWbILOj7_k9HsPZbTbvngYBhch7YululVcGsXain56hm7SPsd6g0pJJiU1ajK8PFA-p1IyhMeJKbFT0HYK2j4FXTs-_LvoI_832Qq8PwCbMqb8pEuhDGk1_wPWc60E</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1862661978</pqid></control><display><type>article</type><title>Charge-altering releasable transporters (CARTs) for the delivery and release of mRNA in living animals</title><source>MEDLINE</source><source>Jstor Complete Legacy</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>McKinlay, Colin J. ; Vargas, Jessica R. ; Blake, Timothy R. ; Hardy, Jonathan W. ; Kanada, Masamitsu ; Contag, Christopher H. ; Wender, Paul A. ; Waymouth, Robert M.</creator><creatorcontrib>McKinlay, Colin J. ; Vargas, Jessica R. ; Blake, Timothy R. ; Hardy, Jonathan W. ; Kanada, Masamitsu ; Contag, Christopher H. ; Wender, Paul A. ; Waymouth, Robert M. ; Stanford Univ., CA (United States)</creatorcontrib><description>Functional delivery of mRNA to tissues in the body is key to implementing fundamentally new and potentially transformative strategies for vaccination, protein replacement therapy, and genome editing, collectively affecting approaches for the prevention, detection, and treatment of disease. Broadly applicable tools for the efficient delivery of mRNA into cultured cells would advance many areas of research, and effective and safe in vivo mRNA delivery could fundamentally transform clinical practice. Here we report the step-economical synthesis and evaluation of a tunable and effective class of synthetic biodegradable materials: charge-altering releasable transporters (CARTs) for mRNA delivery into cells. CARTs are structurally unique and operate through an unprecedented mechanism, serving initially as oligo(α-amino ester) cations that complex, protect, and deliver mRNA and then change physical properties through a degradative, charge-neutralizing intramolecular rearrangement, leading to intracellular release of functional mRNA and highly efficient protein translation. With demonstrated utility in both cultured cells and animals, this mRNA delivery technology should be broadly applicable to numerous research and therapeutic applications.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1614193114</identifier><identifier>PMID: 28069945</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; BASIC BIOLOGICAL SCIENCES ; Biocompatible Materials - administration & dosage ; Biodegradable materials ; Biological Sciences ; Carbocyanines ; Cell culture ; Cell Line ; Cell Line, Tumor ; cell-penetrating ; Cells, Cultured ; Female ; gene therapy ; Gene Transfer Techniques ; Green Fluorescent Proteins - genetics ; Humans ; Medical treatment ; Mesenchymal Stem Cells - metabolism ; Mice, Inbred BALB C ; nanoparticle ; organocatalysis ; Physical Sciences ; PNAS Plus ; Proteins ; Ribonucleic acid ; RNA ; RNA, Messenger - administration & dosage ; stimuli-responsive</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2017-01, Vol.114 (4), p.E448-E456</ispartof><rights>Volumes 1–89 and 106–114, copyright as a collective work only; author(s) retains copyright to individual articles</rights><rights>Copyright National Academy of Sciences Jan 24, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c536t-2b9a929bb2d427c0b5088896a674f8177e309754b70a172fffb80b54b310a1613</citedby><cites>FETCH-LOGICAL-c536t-2b9a929bb2d427c0b5088896a674f8177e309754b70a172fffb80b54b310a1613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/26479058$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/26479058$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,724,777,781,800,882,27905,27906,53772,53774,57998,58231</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28069945$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/1338628$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>McKinlay, Colin J.</creatorcontrib><creatorcontrib>Vargas, Jessica R.</creatorcontrib><creatorcontrib>Blake, Timothy R.</creatorcontrib><creatorcontrib>Hardy, Jonathan W.</creatorcontrib><creatorcontrib>Kanada, Masamitsu</creatorcontrib><creatorcontrib>Contag, Christopher H.</creatorcontrib><creatorcontrib>Wender, Paul A.</creatorcontrib><creatorcontrib>Waymouth, Robert M.</creatorcontrib><creatorcontrib>Stanford Univ., CA (United States)</creatorcontrib><title>Charge-altering releasable transporters (CARTs) for the delivery and release of mRNA in living animals</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Functional delivery of mRNA to tissues in the body is key to implementing fundamentally new and potentially transformative strategies for vaccination, protein replacement therapy, and genome editing, collectively affecting approaches for the prevention, detection, and treatment of disease. Broadly applicable tools for the efficient delivery of mRNA into cultured cells would advance many areas of research, and effective and safe in vivo mRNA delivery could fundamentally transform clinical practice. Here we report the step-economical synthesis and evaluation of a tunable and effective class of synthetic biodegradable materials: charge-altering releasable transporters (CARTs) for mRNA delivery into cells. CARTs are structurally unique and operate through an unprecedented mechanism, serving initially as oligo(α-amino ester) cations that complex, protect, and deliver mRNA and then change physical properties through a degradative, charge-neutralizing intramolecular rearrangement, leading to intracellular release of functional mRNA and highly efficient protein translation. With demonstrated utility in both cultured cells and animals, this mRNA delivery technology should be broadly applicable to numerous research and therapeutic applications.</description><subject>Animals</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>Biocompatible Materials - administration & dosage</subject><subject>Biodegradable materials</subject><subject>Biological Sciences</subject><subject>Carbocyanines</subject><subject>Cell culture</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>cell-penetrating</subject><subject>Cells, Cultured</subject><subject>Female</subject><subject>gene therapy</subject><subject>Gene Transfer Techniques</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Humans</subject><subject>Medical treatment</subject><subject>Mesenchymal Stem Cells - metabolism</subject><subject>Mice, Inbred BALB C</subject><subject>nanoparticle</subject><subject>organocatalysis</subject><subject>Physical Sciences</subject><subject>PNAS Plus</subject><subject>Proteins</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Messenger - administration & dosage</subject><subject>stimuli-responsive</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkctrGzEQxkVpaNy0555aRHtJD5votXpcCsb0EQgphPQstPLIXrOWXGkdyH9fLXaTNqcBfb_5NDMfQu8ouaBE8ctddOWCSiqo4ZSKF2hGiaGNFIa8RDNCmGq0YOIUvS5lQwgxrSav0CnTRBoj2hkKi7XLK2jcMELu4wpnGMAV1w2Ax-xi2aVclYLPF_Pbu_IZh5TxuAa8hKG_h_yAXVwemwCngLe3N3PcR1zVyc7FfuuG8gadhFrg7bGeoV_fvt4tfjTXP79fLebXjW-5HBvWGWeY6Tq2FEx50rVEa22kk0oETZUCToxqRaeIo4qFEDpdIdFxWh8k5Wfoy8F3t--2sPQQ6xKD3eU6RX6wyfX2fyX2a7tK97ZlSguuq8HHg0EqY2-L70fwa59iBD9ayrmWbILOj7_k9HsPZbTbvngYBhch7YululVcGsXain56hm7SPsd6g0pJJiU1ajK8PFA-p1IyhMeJKbFT0HYK2j4FXTs-_LvoI_832Qq8PwCbMqb8pEuhDGk1_wPWc60E</recordid><startdate>20170124</startdate><enddate>20170124</enddate><creator>McKinlay, Colin J.</creator><creator>Vargas, Jessica R.</creator><creator>Blake, Timothy R.</creator><creator>Hardy, Jonathan W.</creator><creator>Kanada, Masamitsu</creator><creator>Contag, Christopher H.</creator><creator>Wender, Paul A.</creator><creator>Waymouth, Robert M.</creator><general>National Academy of Sciences</general><general>Proceedings of the National Academy of Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>OTOTI</scope><scope>5PM</scope></search><sort><creationdate>20170124</creationdate><title>Charge-altering releasable transporters (CARTs) for the delivery and release of mRNA in living animals</title><author>McKinlay, Colin J. ; Vargas, Jessica R. ; Blake, Timothy R. ; Hardy, Jonathan W. ; Kanada, Masamitsu ; Contag, Christopher H. ; Wender, Paul A. ; Waymouth, Robert M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c536t-2b9a929bb2d427c0b5088896a674f8177e309754b70a172fffb80b54b310a1613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>BASIC BIOLOGICAL SCIENCES</topic><topic>Biocompatible Materials - administration & dosage</topic><topic>Biodegradable materials</topic><topic>Biological Sciences</topic><topic>Carbocyanines</topic><topic>Cell culture</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>cell-penetrating</topic><topic>Cells, Cultured</topic><topic>Female</topic><topic>gene therapy</topic><topic>Gene Transfer Techniques</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>Humans</topic><topic>Medical treatment</topic><topic>Mesenchymal Stem Cells - metabolism</topic><topic>Mice, Inbred BALB C</topic><topic>nanoparticle</topic><topic>organocatalysis</topic><topic>Physical Sciences</topic><topic>PNAS Plus</topic><topic>Proteins</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Messenger - administration & dosage</topic><topic>stimuli-responsive</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McKinlay, Colin J.</creatorcontrib><creatorcontrib>Vargas, Jessica R.</creatorcontrib><creatorcontrib>Blake, Timothy R.</creatorcontrib><creatorcontrib>Hardy, Jonathan W.</creatorcontrib><creatorcontrib>Kanada, Masamitsu</creatorcontrib><creatorcontrib>Contag, Christopher H.</creatorcontrib><creatorcontrib>Wender, Paul A.</creatorcontrib><creatorcontrib>Waymouth, Robert M.</creatorcontrib><creatorcontrib>Stanford Univ., CA (United States)</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McKinlay, Colin J.</au><au>Vargas, Jessica R.</au><au>Blake, Timothy R.</au><au>Hardy, Jonathan W.</au><au>Kanada, Masamitsu</au><au>Contag, Christopher H.</au><au>Wender, Paul A.</au><au>Waymouth, Robert M.</au><aucorp>Stanford Univ., CA (United States)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Charge-altering releasable transporters (CARTs) for the delivery and release of mRNA in living animals</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2017-01-24</date><risdate>2017</risdate><volume>114</volume><issue>4</issue><spage>E448</spage><epage>E456</epage><pages>E448-E456</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Functional delivery of mRNA to tissues in the body is key to implementing fundamentally new and potentially transformative strategies for vaccination, protein replacement therapy, and genome editing, collectively affecting approaches for the prevention, detection, and treatment of disease. Broadly applicable tools for the efficient delivery of mRNA into cultured cells would advance many areas of research, and effective and safe in vivo mRNA delivery could fundamentally transform clinical practice. Here we report the step-economical synthesis and evaluation of a tunable and effective class of synthetic biodegradable materials: charge-altering releasable transporters (CARTs) for mRNA delivery into cells. CARTs are structurally unique and operate through an unprecedented mechanism, serving initially as oligo(α-amino ester) cations that complex, protect, and deliver mRNA and then change physical properties through a degradative, charge-neutralizing intramolecular rearrangement, leading to intracellular release of functional mRNA and highly efficient protein translation. With demonstrated utility in both cultured cells and animals, this mRNA delivery technology should be broadly applicable to numerous research and therapeutic applications.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>28069945</pmid><doi>10.1073/pnas.1614193114</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2017-01, Vol.114 (4), p.E448-E456 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5278438 |
| source | MEDLINE; Jstor Complete Legacy; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals BASIC BIOLOGICAL SCIENCES Biocompatible Materials - administration & dosage Biodegradable materials Biological Sciences Carbocyanines Cell culture Cell Line Cell Line, Tumor cell-penetrating Cells, Cultured Female gene therapy Gene Transfer Techniques Green Fluorescent Proteins - genetics Humans Medical treatment Mesenchymal Stem Cells - metabolism Mice, Inbred BALB C nanoparticle organocatalysis Physical Sciences PNAS Plus Proteins Ribonucleic acid RNA RNA, Messenger - administration & dosage stimuli-responsive |
| title | Charge-altering releasable transporters (CARTs) for the delivery and release of mRNA in living animals |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T08%3A03%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Charge-altering%20releasable%20transporters%20(CARTs)%20for%20the%20delivery%20and%20release%20of%20mRNA%20in%20living%20animals&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=McKinlay,%20Colin%20J.&rft.aucorp=Stanford%20Univ.,%20CA%20(United%20States)&rft.date=2017-01-24&rft.volume=114&rft.issue=4&rft.spage=E448&rft.epage=E456&rft.pages=E448-E456&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.1614193114&rft_dat=%3Cjstor_pubme%3E26479058%3C/jstor_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1862661978&rft_id=info:pmid/28069945&rft_jstor_id=26479058&rfr_iscdi=true |