Rational design of lipid nanoparticles for enabling gene therapies
Lipid nanoparticle (LNP) technology is increasingly enabling RNA-based gene therapies that can potentially be used to treat most diseases. Further, these LNP RNA therapeutics can be designed and manufactured in a matter of weeks, allowing personalized medicines that can be produced in a time frame r...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050125001135 |
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| author | Cedric A. Brimacombe Jayesh A. Kulkarni Miffy H.Y. Cheng Kevin An Dominik Witzigmann Pieter R. Cullis |
| author_facet | Cedric A. Brimacombe Jayesh A. Kulkarni Miffy H.Y. Cheng Kevin An Dominik Witzigmann Pieter R. Cullis |
| author_sort | Cedric A. Brimacombe |
| collection | DOAJ |
| description | Lipid nanoparticle (LNP) technology is increasingly enabling RNA-based gene therapies that can potentially be used to treat most diseases. Further, these LNP RNA therapeutics can be designed and manufactured in a matter of weeks, allowing personalized medicines that can be produced in a time frame relevant to individuals suffering from terminal diseases. Here, we focus on the rational design principles that have successfully enabled LNP small interfering RNA (siRNA) formulations to silence pathogenic genes in the liver and LNP mRNA formulations to express therapeutic proteins for vaccines and gene therapies. These principles have evolved from over 50 years of research into the physical properties and functional roles of lipids in membranes as well as experience gained developing LNP systems for delivery of small molecule drugs. It is expected that these rational design principles will be successful in enabling most forms of gene therapies. |
| format | Article |
| id | doaj-art-4cf2f5940bc84a7b8eb99bb96389fe98 |
| institution | DOAJ |
| issn | 2329-0501 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj-art-4cf2f5940bc84a7b8eb99bb96389fe982025-08-20T03:17:03ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012025-09-0133310151810.1016/j.omtm.2025.101518Rational design of lipid nanoparticles for enabling gene therapiesCedric A. Brimacombe0Jayesh A. Kulkarni1Miffy H.Y. Cheng2Kevin An3Dominik Witzigmann4Pieter R. Cullis5Polymorphic BioSciences Inc, 2665 East Mall, Vancouver, BC V6T 1Z4, Canada; Corresponding author: Cedric Brimacombe, Polymorphic BioSciences Inc, Vancouver, BC V6T 1Z4, Canada.NanoVation Therapeutics, 2665 East Mall, Vancouver, BC V6T 1Z4, CanadaDepartment of Biochemistry and Molecular Biology, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, CanadaNanoVation Therapeutics, 2665 East Mall, Vancouver, BC V6T 1Z4, CanadaNanoVation Therapeutics, 2665 East Mall, Vancouver, BC V6T 1Z4, CanadaPolymorphic BioSciences Inc, 2665 East Mall, Vancouver, BC V6T 1Z4, Canada; NanoVation Therapeutics, 2665 East Mall, Vancouver, BC V6T 1Z4, Canada; Department of Biochemistry and Molecular Biology, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; Corresponding author: Pieter R Cullis, Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada.Lipid nanoparticle (LNP) technology is increasingly enabling RNA-based gene therapies that can potentially be used to treat most diseases. Further, these LNP RNA therapeutics can be designed and manufactured in a matter of weeks, allowing personalized medicines that can be produced in a time frame relevant to individuals suffering from terminal diseases. Here, we focus on the rational design principles that have successfully enabled LNP small interfering RNA (siRNA) formulations to silence pathogenic genes in the liver and LNP mRNA formulations to express therapeutic proteins for vaccines and gene therapies. These principles have evolved from over 50 years of research into the physical properties and functional roles of lipids in membranes as well as experience gained developing LNP systems for delivery of small molecule drugs. It is expected that these rational design principles will be successful in enabling most forms of gene therapies.http://www.sciencedirect.com/science/article/pii/S2329050125001135lipid nanoparticlemessenger RNAsiRNArational designendosomal escapegene therapy |
| spellingShingle | Cedric A. Brimacombe Jayesh A. Kulkarni Miffy H.Y. Cheng Kevin An Dominik Witzigmann Pieter R. Cullis Rational design of lipid nanoparticles for enabling gene therapies Molecular Therapy: Methods & Clinical Development lipid nanoparticle messenger RNA siRNA rational design endosomal escape gene therapy |
| title | Rational design of lipid nanoparticles for enabling gene therapies |
| title_full | Rational design of lipid nanoparticles for enabling gene therapies |
| title_fullStr | Rational design of lipid nanoparticles for enabling gene therapies |
| title_full_unstemmed | Rational design of lipid nanoparticles for enabling gene therapies |
| title_short | Rational design of lipid nanoparticles for enabling gene therapies |
| title_sort | rational design of lipid nanoparticles for enabling gene therapies |
| topic | lipid nanoparticle messenger RNA siRNA rational design endosomal escape gene therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2329050125001135 |
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