CleanCap M6 inhibits decapping of exogenously delivered IVT mRNA
Co-transcriptional capping allows exogenous mRNAs to yield robust protein expression. Identifying additional mRNA modifications that further boost protein output will be crucial for developing more efficacious mRNA therapies. Using in vitro approaches, we found that the co-transcriptional cap analog...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253125000101 |
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| author | Zachary F. Mandell Andrew Ujita Jordana Henderson Anthony Truong Coleen Vo Farinaz Rezvani Nona Abolhassani Alexandre Lebedev Chunping Xu Inna Koukhareva Stephanie Ramos Kate Broderick Benjamin Hudson Jeff Coller |
| author_facet | Zachary F. Mandell Andrew Ujita Jordana Henderson Anthony Truong Coleen Vo Farinaz Rezvani Nona Abolhassani Alexandre Lebedev Chunping Xu Inna Koukhareva Stephanie Ramos Kate Broderick Benjamin Hudson Jeff Coller |
| author_sort | Zachary F. Mandell |
| collection | DOAJ |
| description | Co-transcriptional capping allows exogenous mRNAs to yield robust protein expression. Identifying additional mRNA modifications that further boost protein output will be crucial for developing more efficacious mRNA therapies. Using in vitro approaches, we found that the co-transcriptional cap analog m7G3'OMepppm6A2′OMepG, CleanCap M6, resists enzymatic decapping and that this decreased susceptibility to decapping correlated with substantially increased protein expression in vivo compared to mRNAs capped using existing industry standards. |
| format | Article |
| id | doaj-art-eac836ecf6b545f380bb2fbba8807d71 |
| institution | Kabale University |
| issn | 2162-2531 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj-art-eac836ecf6b545f380bb2fbba8807d712025-02-02T05:27:05ZengElsevierMolecular Therapy: Nucleic Acids2162-25312025-03-01361102456CleanCap M6 inhibits decapping of exogenously delivered IVT mRNAZachary F. Mandell0Andrew Ujita1Jordana Henderson2Anthony Truong3Coleen Vo4Farinaz Rezvani5Nona Abolhassani6Alexandre Lebedev7Chunping Xu8Inna Koukhareva9Stephanie Ramos10Kate Broderick11Benjamin Hudson12Jeff Coller13RNA Innovation Center, Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USATriLink BioTechnologies, Part of Maravai LifeSciences, San Diego, CA 92121, USATriLink BioTechnologies, Part of Maravai LifeSciences, San Diego, CA 92121, USATriLink BioTechnologies, Part of Maravai LifeSciences, San Diego, CA 92121, USATriLink BioTechnologies, Part of Maravai LifeSciences, San Diego, CA 92121, USATriLink BioTechnologies, Part of Maravai LifeSciences, San Diego, CA 92121, USATriLink BioTechnologies, Part of Maravai LifeSciences, San Diego, CA 92121, USATriLink BioTechnologies, Part of Maravai LifeSciences, San Diego, CA 92121, USATriLink BioTechnologies, Part of Maravai LifeSciences, San Diego, CA 92121, USATriLink BioTechnologies, Part of Maravai LifeSciences, San Diego, CA 92121, USATriLink BioTechnologies, Part of Maravai LifeSciences, San Diego, CA 92121, USATriLink BioTechnologies, Part of Maravai LifeSciences, San Diego, CA 92121, USATriLink BioTechnologies, Part of Maravai LifeSciences, San Diego, CA 92121, USARNA Innovation Center, Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA; Corresponding author: Jeff Coller, RNA Innovation Center, Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.Co-transcriptional capping allows exogenous mRNAs to yield robust protein expression. Identifying additional mRNA modifications that further boost protein output will be crucial for developing more efficacious mRNA therapies. Using in vitro approaches, we found that the co-transcriptional cap analog m7G3'OMepppm6A2′OMepG, CleanCap M6, resists enzymatic decapping and that this decreased susceptibility to decapping correlated with substantially increased protein expression in vivo compared to mRNAs capped using existing industry standards.http://www.sciencedirect.com/science/article/pii/S2162253125000101MT: Delivery StrategiesmRNAmRNA medicinesmRNA therapeuticsmRNA durabilitymRNA stability |
| spellingShingle | Zachary F. Mandell Andrew Ujita Jordana Henderson Anthony Truong Coleen Vo Farinaz Rezvani Nona Abolhassani Alexandre Lebedev Chunping Xu Inna Koukhareva Stephanie Ramos Kate Broderick Benjamin Hudson Jeff Coller CleanCap M6 inhibits decapping of exogenously delivered IVT mRNA Molecular Therapy: Nucleic Acids MT: Delivery Strategies mRNA mRNA medicines mRNA therapeutics mRNA durability mRNA stability |
| title | CleanCap M6 inhibits decapping of exogenously delivered IVT mRNA |
| title_full | CleanCap M6 inhibits decapping of exogenously delivered IVT mRNA |
| title_fullStr | CleanCap M6 inhibits decapping of exogenously delivered IVT mRNA |
| title_full_unstemmed | CleanCap M6 inhibits decapping of exogenously delivered IVT mRNA |
| title_short | CleanCap M6 inhibits decapping of exogenously delivered IVT mRNA |
| title_sort | cleancap m6 inhibits decapping of exogenously delivered ivt mrna |
| topic | MT: Delivery Strategies mRNA mRNA medicines mRNA therapeutics mRNA durability mRNA stability |
| url | http://www.sciencedirect.com/science/article/pii/S2162253125000101 |
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