File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Strong Immune Responses Induced by Direct Local Injections of Modified mRNA-Lipid Nanocomplexes

TitleStrong Immune Responses Induced by Direct Local Injections of Modified mRNA-Lipid Nanocomplexes
Authors
KeywordsmRNA therapy
vaccines
cationic liposomal delivery
nanocomplexes
T- cell responses
Issue Date2020
PublisherElsevier (Cell Press): OAJ. The Journal's web site is located at http://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content
Citation
Molecular Therapy - Nucleic Acids, 2020, v. 19, p. 1098-1109 How to Cite?
AbstractArticle Info Figures Tables Related Articles In vitro transcribed mRNAs hold the promises of many medical applications in disease prevention and treatment, such as replacement or supplement of missing or inadequately expressed endogenous proteins and as preventive vaccines against infectious diseases, therapeutic vaccines, or other protein-based biopharmaceutics for cancer therapy. A safe and efficient delivery system for mRNA is crucial to the success of mRNA therapeutic applications. In this study, we report that InstantFECT, a liposome-based transfection reagent, can pack pseudouridine-incorporated mRNA into nanocomplexes that are highly efficient in mediating in vivo transfection in multiple organs after local delivery. High levels of expression of EGFP and luciferase reporters after intratumoral and intramuscular injections were observed, which lasted for up to 96 hrs. Immunogenicity of antigens encoded by mRNA delivered with nanocomplex was investigated by subcutaneous delivery of modified mRNAs encoding Staphylococcus aureus adenosine synthase A (AdsA) and a model tumor-associated antigen ovalbumin (OVA). Strong T cell responses were provoked by both mRNAs delivered. Therapeutic and protective treatment with the OVA mRNA-liposome nanocomplex significantly inhibited B16-OVA tumor progression and increased mouse survival. There was no sign of obvious toxicity related to the treatment both in tissue culture and in mice. An intravenous injection of the same dosage of the modified mRNA-lipid nanocomplex showed minimal transfection in major organs, indicating an excellent safety feature as the gene transfer occurred only at the injection sites, whereas intravenous (i.v.) injection with the same amount of mRNA complexed with a commercial transfection reagent Trans-IT showed luciferase expression in the spleen. In summary, InstantFECT cationic liposomes provide a safe and efficient in vivo locoregional delivery of mRNA and could be a useful tool for basic research and for the development of mRNA-based therapies.
Persistent Identifierhttp://hdl.handle.net/10722/287588
ISSN
2019 Impact Factor: 7.032
2015 SCImago Journal Rankings: 2.320
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorARYA, S-
dc.contributor.authorLin, Q-
dc.contributor.authorZhou, NAN-
dc.contributor.authorGao, XIANG-
dc.contributor.authorHuang, JD-
dc.date.accessioned2020-10-05T12:00:16Z-
dc.date.available2020-10-05T12:00:16Z-
dc.date.issued2020-
dc.identifier.citationMolecular Therapy - Nucleic Acids, 2020, v. 19, p. 1098-1109-
dc.identifier.issn2162-2531-
dc.identifier.urihttp://hdl.handle.net/10722/287588-
dc.description.abstractArticle Info Figures Tables Related Articles In vitro transcribed mRNAs hold the promises of many medical applications in disease prevention and treatment, such as replacement or supplement of missing or inadequately expressed endogenous proteins and as preventive vaccines against infectious diseases, therapeutic vaccines, or other protein-based biopharmaceutics for cancer therapy. A safe and efficient delivery system for mRNA is crucial to the success of mRNA therapeutic applications. In this study, we report that InstantFECT, a liposome-based transfection reagent, can pack pseudouridine-incorporated mRNA into nanocomplexes that are highly efficient in mediating in vivo transfection in multiple organs after local delivery. High levels of expression of EGFP and luciferase reporters after intratumoral and intramuscular injections were observed, which lasted for up to 96 hrs. Immunogenicity of antigens encoded by mRNA delivered with nanocomplex was investigated by subcutaneous delivery of modified mRNAs encoding Staphylococcus aureus adenosine synthase A (AdsA) and a model tumor-associated antigen ovalbumin (OVA). Strong T cell responses were provoked by both mRNAs delivered. Therapeutic and protective treatment with the OVA mRNA-liposome nanocomplex significantly inhibited B16-OVA tumor progression and increased mouse survival. There was no sign of obvious toxicity related to the treatment both in tissue culture and in mice. An intravenous injection of the same dosage of the modified mRNA-lipid nanocomplex showed minimal transfection in major organs, indicating an excellent safety feature as the gene transfer occurred only at the injection sites, whereas intravenous (i.v.) injection with the same amount of mRNA complexed with a commercial transfection reagent Trans-IT showed luciferase expression in the spleen. In summary, InstantFECT cationic liposomes provide a safe and efficient in vivo locoregional delivery of mRNA and could be a useful tool for basic research and for the development of mRNA-based therapies.-
dc.languageeng-
dc.publisherElsevier (Cell Press): OAJ. The Journal's web site is located at http://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content-
dc.relation.ispartofMolecular Therapy - Nucleic Acids-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectmRNA therapy-
dc.subjectvaccines-
dc.subjectcationic liposomal delivery-
dc.subjectnanocomplexes-
dc.subjectT- cell responses-
dc.titleStrong Immune Responses Induced by Direct Local Injections of Modified mRNA-Lipid Nanocomplexes-
dc.typeArticle-
dc.identifier.emailLin, Q: qiubin@hku.hk-
dc.identifier.emailHuang, JD: jdhuang@hku.hk-
dc.identifier.authorityHuang, JD=rp00451-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.omtn.2019.12.044-
dc.identifier.pmid32059336-
dc.identifier.pmcidPMC7016160-
dc.identifier.scopuseid_2-s2.0-85079175379-
dc.identifier.hkuros315546-
dc.identifier.volume19-
dc.identifier.spage1098-
dc.identifier.epage1109-
dc.identifier.isiWOS:000519557700090-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl2162-2531-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats