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Ionizable lipid nanoparticles for in utero mRNA delivery
- Source :
- Science Advances
- Publication Year :
- 2019
-
Abstract
- Lipid nanoparticles deliver mRNA to mouse fetuses, which may ultimately enable in utero therapy to treat fetal genetic diseases.<br />Clinical advances enable the prenatal diagnosis of genetic diseases that are candidates for gene and enzyme therapies such as messenger RNA (mRNA)–mediated protein replacement. Prenatal mRNA therapies can treat disease before the onset of irreversible pathology with high therapeutic efficacy and safety due to the small fetal size, immature immune system, and abundance of progenitor cells. However, the development of nonviral platforms for prenatal delivery is nascent. We developed a library of ionizable lipid nanoparticles (LNPs) for in utero mRNA delivery to mouse fetuses. We screened LNPs for luciferase mRNA delivery and identified formulations that accumulate within fetal livers, lungs, and intestines with higher efficiency and safety compared to benchmark delivery systems, DLin-MC3-DMA and jetPEI. We demonstrate that LNPs can deliver mRNAs to induce hepatic production of therapeutic secreted proteins. These LNPs may provide a platform for in utero mRNA delivery for protein replacement and gene editing.
- Subjects :
- 02 engineering and technology
03 medical and health sciences
Mice
Immune system
Medicine
Animals
Luciferase
Health and Medicine
RNA, Messenger
Progenitor cell
Gene
reproductive and urinary physiology
Research Articles
030304 developmental biology
Gene Editing
0303 health sciences
Fetus
Messenger RNA
Multidisciplinary
business.industry
SciAdv r-articles
Life Sciences
021001 nanoscience & nanotechnology
Cell biology
Secretory protein
In utero
embryonic structures
Liposomes
Nanoparticles
0210 nano-technology
business
Research Article
Subjects
Details
- ISSN :
- 23752548
- Volume :
- 7
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Science advances
- Accession number :
- edsair.doi.dedup.....142da725cb734602186e5fb361318153