Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune responses in vivo
Vaccination with in vitro transcribed RNA coding for tumor antigens is considered a promising approach for cancer immunotherapy and has already entered human clinical testing. One of the basic objectives for development of RNA as a drug is the optimization of immunobioavailability of the encoded ant...
Gespeichert in:
| Veröffentlicht in: | Gene therapy 2010-08, Vol.17 (8), p.961-971 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 971 |
|---|---|
| container_issue | 8 |
| container_start_page | 961 |
| container_title | Gene therapy |
| container_volume | 17 |
| creator | Kuhn, A N Diken, M Kreiter, S Selmi, A Kowalska, J Jemielity, J Darzynkiewicz, E Huber, C Türeci, Ö Sahin, U |
| description | Vaccination with
in vitro
transcribed RNA coding for tumor antigens is considered a promising approach for cancer immunotherapy and has already entered human clinical testing. One of the basic objectives for development of RNA as a drug is the optimization of immunobioavailability of the encoded antigen
in vivo
. By analyzing the effect of different synthetic 5′ mRNA cap analogs on the kinetics of the encoded protein, we found that m
2
7,2′−O
Gpp
S
pG (β-S-ARCA) phosphorothioate caps, in particular the D1 diastereoisomer, profoundly enhance RNA stability and translational efficiency in immature but not mature dendritic cells. Moreover,
in vivo
delivery of the antigen as β-S-ARCA(D1)-capped RNA species is superior for protein expression and for efficient priming and expansion of naïve antigen-specific T cells in mice. Our findings establish 5′ mRNA cap analogs as yet another module for tuning immunopharmacological properties of recombinant antigen-encoding RNA for vaccination purposes. |
| doi_str_mv | 10.1038/gt.2010.52 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_754887462</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A235194618</galeid><sourcerecordid>A235194618</sourcerecordid><originalsourceid>FETCH-LOGICAL-c673t-88d853493264c2bb672b381f4badaec875801265731c563922bfeb2b37c62683</originalsourceid><addsrcrecordid>eNqF0s2O0zAQAOAIgdiycOEBkAUCBKjFf3GcY7XiZ6UVoGXvkeNMUq9SO2s7FX0g3hOHFkrRIpSDlfibcWY8WfaY4AXBTL7t4oLi9JLTO9mM8ELMcy7o3WyGS1HOC0LlSfYghGuMMS8kvZ-dUMwJLhmZZd-_rFwYVs67uDJORUBaDUhZ1bsuIGO1BxUAhahq05u4TVsNil7Z0KtoXHII2tZoA1ZvkWvR5acl2iitjYUpHpn1WsXRA2rANt5Eo5GGvg8_ExnbjDplHwfwxvkJjxaQhzA4G3YJNmbjHmb3WtUHeLRfT7Or9--uzj7OLz5_OD9bXsy1KFicS9nInPGSUcE1rWtR0JpJ0vJaNQq0LHKJCRV5wYjOBSsprVuokym0oEKy0-zlLu3g3c0IIVZrE6a_VRbcGKoi51IWqbf_l1yWnGHOknz6l7x2o099mxDNiSzEhJ79C6VSuOCUC3xQneqhMrZ16SL0dHC1pCwnJRdkKmJxi0pPA2ujnYXWpO9HAa-OApKJ8C12agyhOv96eWxf_GFXoPq4Cq4fp1EIx_D1DmrvQvDQVoM3a-W3FcHVNLVVF6tpaqt86uaTffljvYbmN_01pgk83wMVtOrbNH_ahINjuMip5Mm92bmQtmwH_tDHW479Ae4iAJ4</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2644642460</pqid></control><display><type>article</type><title>Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune responses in vivo</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Kuhn, A N ; Diken, M ; Kreiter, S ; Selmi, A ; Kowalska, J ; Jemielity, J ; Darzynkiewicz, E ; Huber, C ; Türeci, Ö ; Sahin, U</creator><creatorcontrib>Kuhn, A N ; Diken, M ; Kreiter, S ; Selmi, A ; Kowalska, J ; Jemielity, J ; Darzynkiewicz, E ; Huber, C ; Türeci, Ö ; Sahin, U</creatorcontrib><description>Vaccination with
in vitro
transcribed RNA coding for tumor antigens is considered a promising approach for cancer immunotherapy and has already entered human clinical testing. One of the basic objectives for development of RNA as a drug is the optimization of immunobioavailability of the encoded antigen
in vivo
. By analyzing the effect of different synthetic 5′ mRNA cap analogs on the kinetics of the encoded protein, we found that m
2
7,2′−O
Gpp
S
pG (β-S-ARCA) phosphorothioate caps, in particular the D1 diastereoisomer, profoundly enhance RNA stability and translational efficiency in immature but not mature dendritic cells. Moreover,
in vivo
delivery of the antigen as β-S-ARCA(D1)-capped RNA species is superior for protein expression and for efficient priming and expansion of naïve antigen-specific T cells in mice. Our findings establish 5′ mRNA cap analogs as yet another module for tuning immunopharmacological properties of recombinant antigen-encoding RNA for vaccination purposes.</description><identifier>ISSN: 0969-7128</identifier><identifier>EISSN: 1476-5462</identifier><identifier>DOI: 10.1038/gt.2010.52</identifier><identifier>PMID: 20410931</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/154/436 ; 631/250 ; 631/250/2504/133 ; 631/61/51/2293 ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Antigen (tumor-associated) ; Antigen Presentation ; Antigens ; Applied cell therapy and gene therapy ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Biotechnology ; Cancer ; Cancer immunotherapy ; Cancer Vaccines - genetics ; Cancer Vaccines - immunology ; Cancer Vaccines - metabolism ; Cell Biology ; Dendritic cells ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Gene Therapy ; Genes, Reporter ; Genetic aspects ; Half-Life ; Health aspects ; Health. Pharmaceutical industry ; Human Genetics ; Humans ; Immune response ; Immunization ; Immunotherapy ; Industrial applications and implications. Economical aspects ; Kinetics ; Luciferases - analysis ; Lymphocytes T ; Medical sciences ; Messenger RNA ; mRNA ; Nanotechnology ; original-article ; Phosphorothioate ; Phosphorothioate Oligonucleotides - chemistry ; Physiological aspects ; Protein Biosynthesis ; Ribonucleic acid ; RNA ; RNA - chemistry ; RNA Cap Analogs - chemistry ; RNA Stability ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Translation ; Tumors ; Vaccines, Synthetic - immunology ; Vaccines, Synthetic - metabolism ; Viral vaccines</subject><ispartof>Gene therapy, 2010-08, Vol.17 (8), p.961-971</ispartof><rights>Macmillan Publishers Limited 2010</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2010 Nature Publishing Group</rights><rights>Macmillan Publishers Limited 2010.</rights><rights>Copyright Nature Publishing Group Aug 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c673t-88d853493264c2bb672b381f4badaec875801265731c563922bfeb2b37c62683</citedby><cites>FETCH-LOGICAL-c673t-88d853493264c2bb672b381f4badaec875801265731c563922bfeb2b37c62683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23075284$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20410931$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kuhn, A N</creatorcontrib><creatorcontrib>Diken, M</creatorcontrib><creatorcontrib>Kreiter, S</creatorcontrib><creatorcontrib>Selmi, A</creatorcontrib><creatorcontrib>Kowalska, J</creatorcontrib><creatorcontrib>Jemielity, J</creatorcontrib><creatorcontrib>Darzynkiewicz, E</creatorcontrib><creatorcontrib>Huber, C</creatorcontrib><creatorcontrib>Türeci, Ö</creatorcontrib><creatorcontrib>Sahin, U</creatorcontrib><title>Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune responses in vivo</title><title>Gene therapy</title><addtitle>Gene Ther</addtitle><addtitle>Gene Ther</addtitle><description>Vaccination with
in vitro
transcribed RNA coding for tumor antigens is considered a promising approach for cancer immunotherapy and has already entered human clinical testing. One of the basic objectives for development of RNA as a drug is the optimization of immunobioavailability of the encoded antigen
in vivo
. By analyzing the effect of different synthetic 5′ mRNA cap analogs on the kinetics of the encoded protein, we found that m
2
7,2′−O
Gpp
S
pG (β-S-ARCA) phosphorothioate caps, in particular the D1 diastereoisomer, profoundly enhance RNA stability and translational efficiency in immature but not mature dendritic cells. Moreover,
in vivo
delivery of the antigen as β-S-ARCA(D1)-capped RNA species is superior for protein expression and for efficient priming and expansion of naïve antigen-specific T cells in mice. Our findings establish 5′ mRNA cap analogs as yet another module for tuning immunopharmacological properties of recombinant antigen-encoding RNA for vaccination purposes.</description><subject>631/154/436</subject><subject>631/250</subject><subject>631/250/2504/133</subject><subject>631/61/51/2293</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Antigen (tumor-associated)</subject><subject>Antigen Presentation</subject><subject>Antigens</subject><subject>Applied cell therapy and gene therapy</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Cancer</subject><subject>Cancer immunotherapy</subject><subject>Cancer Vaccines - genetics</subject><subject>Cancer Vaccines - immunology</subject><subject>Cancer Vaccines - metabolism</subject><subject>Cell Biology</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Gene Therapy</subject><subject>Genes, Reporter</subject><subject>Genetic aspects</subject><subject>Half-Life</subject><subject>Health aspects</subject><subject>Health. Pharmaceutical industry</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunization</subject><subject>Immunotherapy</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Kinetics</subject><subject>Luciferases - analysis</subject><subject>Lymphocytes T</subject><subject>Medical sciences</subject><subject>Messenger RNA</subject><subject>mRNA</subject><subject>Nanotechnology</subject><subject>original-article</subject><subject>Phosphorothioate</subject><subject>Phosphorothioate Oligonucleotides - chemistry</subject><subject>Physiological aspects</subject><subject>Protein Biosynthesis</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA - chemistry</subject><subject>RNA Cap Analogs - chemistry</subject><subject>RNA Stability</subject><subject>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><subject>Translation</subject><subject>Tumors</subject><subject>Vaccines, Synthetic - immunology</subject><subject>Vaccines, Synthetic - metabolism</subject><subject>Viral vaccines</subject><issn>0969-7128</issn><issn>1476-5462</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqF0s2O0zAQAOAIgdiycOEBkAUCBKjFf3GcY7XiZ6UVoGXvkeNMUq9SO2s7FX0g3hOHFkrRIpSDlfibcWY8WfaY4AXBTL7t4oLi9JLTO9mM8ELMcy7o3WyGS1HOC0LlSfYghGuMMS8kvZ-dUMwJLhmZZd-_rFwYVs67uDJORUBaDUhZ1bsuIGO1BxUAhahq05u4TVsNil7Z0KtoXHII2tZoA1ZvkWvR5acl2iitjYUpHpn1WsXRA2rANt5Eo5GGvg8_ExnbjDplHwfwxvkJjxaQhzA4G3YJNmbjHmb3WtUHeLRfT7Or9--uzj7OLz5_OD9bXsy1KFicS9nInPGSUcE1rWtR0JpJ0vJaNQq0LHKJCRV5wYjOBSsprVuokym0oEKy0-zlLu3g3c0IIVZrE6a_VRbcGKoi51IWqbf_l1yWnGHOknz6l7x2o099mxDNiSzEhJ79C6VSuOCUC3xQneqhMrZ16SL0dHC1pCwnJRdkKmJxi0pPA2ujnYXWpO9HAa-OApKJ8C12agyhOv96eWxf_GFXoPq4Cq4fp1EIx_D1DmrvQvDQVoM3a-W3FcHVNLVVF6tpaqt86uaTffljvYbmN_01pgk83wMVtOrbNH_ahINjuMip5Mm92bmQtmwH_tDHW479Ae4iAJ4</recordid><startdate>20100801</startdate><enddate>20100801</enddate><creator>Kuhn, A N</creator><creator>Diken, M</creator><creator>Kreiter, S</creator><creator>Selmi, A</creator><creator>Kowalska, J</creator><creator>Jemielity, J</creator><creator>Darzynkiewicz, E</creator><creator>Huber, C</creator><creator>Türeci, Ö</creator><creator>Sahin, U</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>IQODW</scope><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>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>7QO</scope><scope>7T5</scope></search><sort><creationdate>20100801</creationdate><title>Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune responses in vivo</title><author>Kuhn, A N ; Diken, M ; Kreiter, S ; Selmi, A ; Kowalska, J ; Jemielity, J ; Darzynkiewicz, E ; Huber, C ; Türeci, Ö ; Sahin, U</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c673t-88d853493264c2bb672b381f4badaec875801265731c563922bfeb2b37c62683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>631/154/436</topic><topic>631/250</topic><topic>631/250/2504/133</topic><topic>631/61/51/2293</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Antigen (tumor-associated)</topic><topic>Antigen Presentation</topic><topic>Antigens</topic><topic>Applied cell therapy and gene therapy</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Cancer</topic><topic>Cancer immunotherapy</topic><topic>Cancer Vaccines - genetics</topic><topic>Cancer Vaccines - immunology</topic><topic>Cancer Vaccines - metabolism</topic><topic>Cell Biology</topic><topic>Dendritic cells</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression</topic><topic>Gene Therapy</topic><topic>Genes, Reporter</topic><topic>Genetic aspects</topic><topic>Half-Life</topic><topic>Health aspects</topic><topic>Health. Pharmaceutical industry</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immunization</topic><topic>Immunotherapy</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Kinetics</topic><topic>Luciferases - analysis</topic><topic>Lymphocytes T</topic><topic>Medical sciences</topic><topic>Messenger RNA</topic><topic>mRNA</topic><topic>Nanotechnology</topic><topic>original-article</topic><topic>Phosphorothioate</topic><topic>Phosphorothioate Oligonucleotides - chemistry</topic><topic>Physiological aspects</topic><topic>Protein Biosynthesis</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA - chemistry</topic><topic>RNA Cap Analogs - chemistry</topic><topic>RNA Stability</topic><topic>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</topic><topic>Translation</topic><topic>Tumors</topic><topic>Vaccines, Synthetic - immunology</topic><topic>Vaccines, Synthetic - metabolism</topic><topic>Viral vaccines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kuhn, A N</creatorcontrib><creatorcontrib>Diken, M</creatorcontrib><creatorcontrib>Kreiter, S</creatorcontrib><creatorcontrib>Selmi, A</creatorcontrib><creatorcontrib>Kowalska, J</creatorcontrib><creatorcontrib>Jemielity, J</creatorcontrib><creatorcontrib>Darzynkiewicz, E</creatorcontrib><creatorcontrib>Huber, C</creatorcontrib><creatorcontrib>Türeci, Ö</creatorcontrib><creatorcontrib>Sahin, U</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><jtitle>Gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kuhn, A N</au><au>Diken, M</au><au>Kreiter, S</au><au>Selmi, A</au><au>Kowalska, J</au><au>Jemielity, J</au><au>Darzynkiewicz, E</au><au>Huber, C</au><au>Türeci, Ö</au><au>Sahin, U</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune responses in vivo</atitle><jtitle>Gene therapy</jtitle><stitle>Gene Ther</stitle><addtitle>Gene Ther</addtitle><date>2010-08-01</date><risdate>2010</risdate><volume>17</volume><issue>8</issue><spage>961</spage><epage>971</epage><pages>961-971</pages><issn>0969-7128</issn><eissn>1476-5462</eissn><abstract>Vaccination with
in vitro
transcribed RNA coding for tumor antigens is considered a promising approach for cancer immunotherapy and has already entered human clinical testing. One of the basic objectives for development of RNA as a drug is the optimization of immunobioavailability of the encoded antigen
in vivo
. By analyzing the effect of different synthetic 5′ mRNA cap analogs on the kinetics of the encoded protein, we found that m
2
7,2′−O
Gpp
S
pG (β-S-ARCA) phosphorothioate caps, in particular the D1 diastereoisomer, profoundly enhance RNA stability and translational efficiency in immature but not mature dendritic cells. Moreover,
in vivo
delivery of the antigen as β-S-ARCA(D1)-capped RNA species is superior for protein expression and for efficient priming and expansion of naïve antigen-specific T cells in mice. Our findings establish 5′ mRNA cap analogs as yet another module for tuning immunopharmacological properties of recombinant antigen-encoding RNA for vaccination purposes.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>20410931</pmid><doi>10.1038/gt.2010.52</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0969-7128 |
| ispartof | Gene therapy, 2010-08, Vol.17 (8), p.961-971 |
| issn | 0969-7128 1476-5462 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_754887462 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | 631/154/436 631/250 631/250/2504/133 631/61/51/2293 Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Antigen (tumor-associated) Antigen Presentation Antigens Applied cell therapy and gene therapy Biological and medical sciences Biomedical and Life Sciences Biomedicine Biotechnology Cancer Cancer immunotherapy Cancer Vaccines - genetics Cancer Vaccines - immunology Cancer Vaccines - metabolism Cell Biology Dendritic cells Dendritic Cells - immunology Dendritic Cells - metabolism Fundamental and applied biological sciences. Psychology Gene Expression Gene Therapy Genes, Reporter Genetic aspects Half-Life Health aspects Health. Pharmaceutical industry Human Genetics Humans Immune response Immunization Immunotherapy Industrial applications and implications. Economical aspects Kinetics Luciferases - analysis Lymphocytes T Medical sciences Messenger RNA mRNA Nanotechnology original-article Phosphorothioate Phosphorothioate Oligonucleotides - chemistry Physiological aspects Protein Biosynthesis Ribonucleic acid RNA RNA - chemistry RNA Cap Analogs - chemistry RNA Stability Transfusions. Complications. Transfusion reactions. Cell and gene therapy Translation Tumors Vaccines, Synthetic - immunology Vaccines, Synthetic - metabolism Viral vaccines |
| title | Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune responses in vivo |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-21T08%3A58%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Phosphorothioate%20cap%20analogs%20increase%20stability%20and%20translational%20efficiency%20of%20RNA%20vaccines%20in%20immature%20dendritic%20cells%20and%20induce%20superior%20immune%20responses%20in%20vivo&rft.jtitle=Gene%20therapy&rft.au=Kuhn,%20A%20N&rft.date=2010-08-01&rft.volume=17&rft.issue=8&rft.spage=961&rft.epage=971&rft.pages=961-971&rft.issn=0969-7128&rft.eissn=1476-5462&rft_id=info:doi/10.1038/gt.2010.52&rft_dat=%3Cgale_proqu%3EA235194618%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2644642460&rft_id=info:pmid/20410931&rft_galeid=A235194618&rfr_iscdi=true |