mRNA compartmentalization via multimodule DNA nanostructure assembly augments the immunogenicity and efficacy of cancer mRNA vaccine
Messenger RNA (mRNA) vaccine has fueled a great hope for cancer immunotherapy. However, low immunogenicity, caused by inefficient mRNA expression and weak immune stimulation, hampers the efficacy of mRNA vaccines. Here, we present an mRNA compartmentalization-based cancer vaccine, comprising a multi...
Gespeichert in:
| Veröffentlicht in: | Science advances 2024-11, Vol.10 (47), p.eadp3680 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 47 |
| container_start_page | eadp3680 |
| container_title | Science advances |
| container_volume | 10 |
| creator | Guo, Xiaocui Guo, Mengyu Cai, Rong Hu, Mingdi Rao, Le Su, Wen Liu, He Gao, Fene Zhang, Xiaoyu Liu, Jing Chen, Chunying |
| description | Messenger RNA (mRNA) vaccine has fueled a great hope for cancer immunotherapy. However, low immunogenicity, caused by inefficient mRNA expression and weak immune stimulation, hampers the efficacy of mRNA vaccines. Here, we present an mRNA compartmentalization-based cancer vaccine, comprising a multimodule DNA nanostructure (MMDNS)-assembled compartment for efficient mRNA translation via in situ localizing mRNA concentration and relevant reaction molecules. The MMDNS is constructed via programmable DNA hybridization chain reaction (HCR)-based strategy, with integrating antigen-coded mRNA, CpG oligodeoxynucleotides (ODNs), acidic-responsive DNA sequence, and dendritic cells targeting aptamer. MMDNS undergoes in situ assembly in acidic lysosomes to form a micro-sized aggregate, inducing an enhanced CpG ODN adjuvant efficacy. Subsequently, the aggregates escape into cytoplasm, providing a moderate compartment which supports the efficient translation of spatially proximal mRNA transcripts via localizing relevant reaction molecules. The mRNA compartmentalization-based vaccine boosts a strong immune response and effectively inhibits tumor growth and metastasis, offering a robust strategy for cancer immunotherapy. |
| doi_str_mv | 10.1126/sciadv.adp3680 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3132141000</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3132141000</sourcerecordid><originalsourceid>FETCH-LOGICAL-c180t-d326ab8b280d57097b0d30e98721c4e284131702737842df74ed1ef14f2580773</originalsourceid><addsrcrecordid>eNpNkEtLAzEURoMoKurWpWTppjWPmUm6FN8gCqLrIZPc0cgkqXkU6tof7tRWcXUv3PN9Fw5Cx5RMKWXNWdJWmcVUmTlvJNlC-4yLesLqSm7_2_fQUUrvhBBaNU1NZ7toj89q0cha7qMv9_RwjnVwcxWzA5_VYD9VtsHjhVXYlSFbF0wZAF-OoFc-pByLziUCVimB64YlVuV1lU04vwG2zhUfXsFbbfN48wZD31ut9BKHHmvlNUT883ehtLYeDtFOr4YER5t5gF6ur54vbif3jzd3F-f3E00lyRPDWaM62TFJTC3ITHTEcAIzKRjVFTBZUU4FYYILWTHTiwoMhZ5WPaslEYIfoNN17zyGjwIpt84mDcOgPISSWk45oxUdVY3odI3qGFKK0LfzaJ2Ky5aSdiW_XctvN_LHwMmmu3QOzB_-q5p_A4Bjg2Q</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3132141000</pqid></control><display><type>article</type><title>mRNA compartmentalization via multimodule DNA nanostructure assembly augments the immunogenicity and efficacy of cancer mRNA vaccine</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Guo, Xiaocui ; Guo, Mengyu ; Cai, Rong ; Hu, Mingdi ; Rao, Le ; Su, Wen ; Liu, He ; Gao, Fene ; Zhang, Xiaoyu ; Liu, Jing ; Chen, Chunying</creator><creatorcontrib>Guo, Xiaocui ; Guo, Mengyu ; Cai, Rong ; Hu, Mingdi ; Rao, Le ; Su, Wen ; Liu, He ; Gao, Fene ; Zhang, Xiaoyu ; Liu, Jing ; Chen, Chunying</creatorcontrib><description>Messenger RNA (mRNA) vaccine has fueled a great hope for cancer immunotherapy. However, low immunogenicity, caused by inefficient mRNA expression and weak immune stimulation, hampers the efficacy of mRNA vaccines. Here, we present an mRNA compartmentalization-based cancer vaccine, comprising a multimodule DNA nanostructure (MMDNS)-assembled compartment for efficient mRNA translation via in situ localizing mRNA concentration and relevant reaction molecules. The MMDNS is constructed via programmable DNA hybridization chain reaction (HCR)-based strategy, with integrating antigen-coded mRNA, CpG oligodeoxynucleotides (ODNs), acidic-responsive DNA sequence, and dendritic cells targeting aptamer. MMDNS undergoes in situ assembly in acidic lysosomes to form a micro-sized aggregate, inducing an enhanced CpG ODN adjuvant efficacy. Subsequently, the aggregates escape into cytoplasm, providing a moderate compartment which supports the efficient translation of spatially proximal mRNA transcripts via localizing relevant reaction molecules. The mRNA compartmentalization-based vaccine boosts a strong immune response and effectively inhibits tumor growth and metastasis, offering a robust strategy for cancer immunotherapy.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.adp3680</identifier><identifier>PMID: 39576858</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Cancer Vaccines - administration & dosage ; Cancer Vaccines - immunology ; Cell Line, Tumor ; Dendritic Cells - immunology ; DNA - chemistry ; DNA - immunology ; Humans ; Immunogenicity, Vaccine ; Immunotherapy - methods ; Mice ; mRNA Vaccines ; Nanostructures - chemistry ; Neoplasms - immunology ; Neoplasms - therapy ; Oligodeoxyribonucleotides ; RNA, Messenger - genetics ; RNA, Messenger - immunology</subject><ispartof>Science advances, 2024-11, Vol.10 (47), p.eadp3680</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c180t-d326ab8b280d57097b0d30e98721c4e284131702737842df74ed1ef14f2580773</cites><orcidid>0000-0001-6793-5765 ; 0000-0002-5023-9445 ; 0009-0008-2636-452X ; 0000-0002-8740-4600 ; 0000-0002-6027-0315 ; 0000-0002-9953-0073</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39576858$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guo, Xiaocui</creatorcontrib><creatorcontrib>Guo, Mengyu</creatorcontrib><creatorcontrib>Cai, Rong</creatorcontrib><creatorcontrib>Hu, Mingdi</creatorcontrib><creatorcontrib>Rao, Le</creatorcontrib><creatorcontrib>Su, Wen</creatorcontrib><creatorcontrib>Liu, He</creatorcontrib><creatorcontrib>Gao, Fene</creatorcontrib><creatorcontrib>Zhang, Xiaoyu</creatorcontrib><creatorcontrib>Liu, Jing</creatorcontrib><creatorcontrib>Chen, Chunying</creatorcontrib><title>mRNA compartmentalization via multimodule DNA nanostructure assembly augments the immunogenicity and efficacy of cancer mRNA vaccine</title><title>Science advances</title><addtitle>Sci Adv</addtitle><description>Messenger RNA (mRNA) vaccine has fueled a great hope for cancer immunotherapy. However, low immunogenicity, caused by inefficient mRNA expression and weak immune stimulation, hampers the efficacy of mRNA vaccines. Here, we present an mRNA compartmentalization-based cancer vaccine, comprising a multimodule DNA nanostructure (MMDNS)-assembled compartment for efficient mRNA translation via in situ localizing mRNA concentration and relevant reaction molecules. The MMDNS is constructed via programmable DNA hybridization chain reaction (HCR)-based strategy, with integrating antigen-coded mRNA, CpG oligodeoxynucleotides (ODNs), acidic-responsive DNA sequence, and dendritic cells targeting aptamer. MMDNS undergoes in situ assembly in acidic lysosomes to form a micro-sized aggregate, inducing an enhanced CpG ODN adjuvant efficacy. Subsequently, the aggregates escape into cytoplasm, providing a moderate compartment which supports the efficient translation of spatially proximal mRNA transcripts via localizing relevant reaction molecules. The mRNA compartmentalization-based vaccine boosts a strong immune response and effectively inhibits tumor growth and metastasis, offering a robust strategy for cancer immunotherapy.</description><subject>Animals</subject><subject>Cancer Vaccines - administration & dosage</subject><subject>Cancer Vaccines - immunology</subject><subject>Cell Line, Tumor</subject><subject>Dendritic Cells - immunology</subject><subject>DNA - chemistry</subject><subject>DNA - immunology</subject><subject>Humans</subject><subject>Immunogenicity, Vaccine</subject><subject>Immunotherapy - methods</subject><subject>Mice</subject><subject>mRNA Vaccines</subject><subject>Nanostructures - chemistry</subject><subject>Neoplasms - immunology</subject><subject>Neoplasms - therapy</subject><subject>Oligodeoxyribonucleotides</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - immunology</subject><issn>2375-2548</issn><issn>2375-2548</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkEtLAzEURoMoKurWpWTppjWPmUm6FN8gCqLrIZPc0cgkqXkU6tof7tRWcXUv3PN9Fw5Cx5RMKWXNWdJWmcVUmTlvJNlC-4yLesLqSm7_2_fQUUrvhBBaNU1NZ7toj89q0cha7qMv9_RwjnVwcxWzA5_VYD9VtsHjhVXYlSFbF0wZAF-OoFc-pByLziUCVimB64YlVuV1lU04vwG2zhUfXsFbbfN48wZD31ut9BKHHmvlNUT883ehtLYeDtFOr4YER5t5gF6ur54vbif3jzd3F-f3E00lyRPDWaM62TFJTC3ITHTEcAIzKRjVFTBZUU4FYYILWTHTiwoMhZ5WPaslEYIfoNN17zyGjwIpt84mDcOgPISSWk45oxUdVY3odI3qGFKK0LfzaJ2Ky5aSdiW_XctvN_LHwMmmu3QOzB_-q5p_A4Bjg2Q</recordid><startdate>20241122</startdate><enddate>20241122</enddate><creator>Guo, Xiaocui</creator><creator>Guo, Mengyu</creator><creator>Cai, Rong</creator><creator>Hu, Mingdi</creator><creator>Rao, Le</creator><creator>Su, Wen</creator><creator>Liu, He</creator><creator>Gao, Fene</creator><creator>Zhang, Xiaoyu</creator><creator>Liu, Jing</creator><creator>Chen, Chunying</creator><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><orcidid>https://orcid.org/0000-0001-6793-5765</orcidid><orcidid>https://orcid.org/0000-0002-5023-9445</orcidid><orcidid>https://orcid.org/0009-0008-2636-452X</orcidid><orcidid>https://orcid.org/0000-0002-8740-4600</orcidid><orcidid>https://orcid.org/0000-0002-6027-0315</orcidid><orcidid>https://orcid.org/0000-0002-9953-0073</orcidid></search><sort><creationdate>20241122</creationdate><title>mRNA compartmentalization via multimodule DNA nanostructure assembly augments the immunogenicity and efficacy of cancer mRNA vaccine</title><author>Guo, Xiaocui ; Guo, Mengyu ; Cai, Rong ; Hu, Mingdi ; Rao, Le ; Su, Wen ; Liu, He ; Gao, Fene ; Zhang, Xiaoyu ; Liu, Jing ; Chen, Chunying</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c180t-d326ab8b280d57097b0d30e98721c4e284131702737842df74ed1ef14f2580773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Cancer Vaccines - administration & dosage</topic><topic>Cancer Vaccines - immunology</topic><topic>Cell Line, Tumor</topic><topic>Dendritic Cells - immunology</topic><topic>DNA - chemistry</topic><topic>DNA - immunology</topic><topic>Humans</topic><topic>Immunogenicity, Vaccine</topic><topic>Immunotherapy - methods</topic><topic>Mice</topic><topic>mRNA Vaccines</topic><topic>Nanostructures - chemistry</topic><topic>Neoplasms - immunology</topic><topic>Neoplasms - therapy</topic><topic>Oligodeoxyribonucleotides</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guo, Xiaocui</creatorcontrib><creatorcontrib>Guo, Mengyu</creatorcontrib><creatorcontrib>Cai, Rong</creatorcontrib><creatorcontrib>Hu, Mingdi</creatorcontrib><creatorcontrib>Rao, Le</creatorcontrib><creatorcontrib>Su, Wen</creatorcontrib><creatorcontrib>Liu, He</creatorcontrib><creatorcontrib>Gao, Fene</creatorcontrib><creatorcontrib>Zhang, Xiaoyu</creatorcontrib><creatorcontrib>Liu, Jing</creatorcontrib><creatorcontrib>Chen, Chunying</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><jtitle>Science advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guo, Xiaocui</au><au>Guo, Mengyu</au><au>Cai, Rong</au><au>Hu, Mingdi</au><au>Rao, Le</au><au>Su, Wen</au><au>Liu, He</au><au>Gao, Fene</au><au>Zhang, Xiaoyu</au><au>Liu, Jing</au><au>Chen, Chunying</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>mRNA compartmentalization via multimodule DNA nanostructure assembly augments the immunogenicity and efficacy of cancer mRNA vaccine</atitle><jtitle>Science advances</jtitle><addtitle>Sci Adv</addtitle><date>2024-11-22</date><risdate>2024</risdate><volume>10</volume><issue>47</issue><spage>eadp3680</spage><pages>eadp3680-</pages><issn>2375-2548</issn><eissn>2375-2548</eissn><abstract>Messenger RNA (mRNA) vaccine has fueled a great hope for cancer immunotherapy. However, low immunogenicity, caused by inefficient mRNA expression and weak immune stimulation, hampers the efficacy of mRNA vaccines. Here, we present an mRNA compartmentalization-based cancer vaccine, comprising a multimodule DNA nanostructure (MMDNS)-assembled compartment for efficient mRNA translation via in situ localizing mRNA concentration and relevant reaction molecules. The MMDNS is constructed via programmable DNA hybridization chain reaction (HCR)-based strategy, with integrating antigen-coded mRNA, CpG oligodeoxynucleotides (ODNs), acidic-responsive DNA sequence, and dendritic cells targeting aptamer. MMDNS undergoes in situ assembly in acidic lysosomes to form a micro-sized aggregate, inducing an enhanced CpG ODN adjuvant efficacy. Subsequently, the aggregates escape into cytoplasm, providing a moderate compartment which supports the efficient translation of spatially proximal mRNA transcripts via localizing relevant reaction molecules. The mRNA compartmentalization-based vaccine boosts a strong immune response and effectively inhibits tumor growth and metastasis, offering a robust strategy for cancer immunotherapy.</abstract><cop>United States</cop><pmid>39576858</pmid><doi>10.1126/sciadv.adp3680</doi><orcidid>https://orcid.org/0000-0001-6793-5765</orcidid><orcidid>https://orcid.org/0000-0002-5023-9445</orcidid><orcidid>https://orcid.org/0009-0008-2636-452X</orcidid><orcidid>https://orcid.org/0000-0002-8740-4600</orcidid><orcidid>https://orcid.org/0000-0002-6027-0315</orcidid><orcidid>https://orcid.org/0000-0002-9953-0073</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2375-2548 |
| ispartof | Science advances, 2024-11, Vol.10 (47), p.eadp3680 |
| issn | 2375-2548 2375-2548 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_3132141000 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Cancer Vaccines - administration & dosage Cancer Vaccines - immunology Cell Line, Tumor Dendritic Cells - immunology DNA - chemistry DNA - immunology Humans Immunogenicity, Vaccine Immunotherapy - methods Mice mRNA Vaccines Nanostructures - chemistry Neoplasms - immunology Neoplasms - therapy Oligodeoxyribonucleotides RNA, Messenger - genetics RNA, Messenger - immunology |
| title | mRNA compartmentalization via multimodule DNA nanostructure assembly augments the immunogenicity and efficacy of cancer mRNA vaccine |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T01%3A44%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=mRNA%20compartmentalization%20via%20multimodule%20DNA%20nanostructure%20assembly%20augments%20the%20immunogenicity%20and%20efficacy%20of%20cancer%20mRNA%20vaccine&rft.jtitle=Science%20advances&rft.au=Guo,%20Xiaocui&rft.date=2024-11-22&rft.volume=10&rft.issue=47&rft.spage=eadp3680&rft.pages=eadp3680-&rft.issn=2375-2548&rft.eissn=2375-2548&rft_id=info:doi/10.1126/sciadv.adp3680&rft_dat=%3Cproquest_cross%3E3132141000%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3132141000&rft_id=info:pmid/39576858&rfr_iscdi=true |