Journal
JOURNAL OF CONTROLLED RELEASE
Volume 291, Issue -, Pages 106-115Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2018.10.015
Keywords
Vascular targeting; mRNA delivery; Apolipoprotein E; Inflammation; Endothelial targeting
Funding
- NIH [NHLBI T32 HL007915, NHLBI RO1 HL128392]
- NIAID of the NIH [R01-AI124429, R01-AI084860]
- amfAR ARCHE grant
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [K08HL138269, T32HL007915, T32HL007971] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI124429] Funding Source: NIH RePORTER
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Systemic administration of lipid nanoparticle (LNP)-encapsulated messenger RNA (mRNA) leads predominantly to hepatic uptake and expression. Here, we conjugated nucleoside-modified mRNA-LNPs with antibodies (Abs) specific to vascular cell adhesion molecule, PECAM-1. Systemic (intravenous) administration of Ab/LNP-mRNAs resulted in profound inhibition of hepatic uptake concomitantly with similar to 200-fold and 25-fold elevation of mRNA delivery and protein expression in the lungs compared to non-targeted counterparts. Unlike hepatic delivery of LNP-mRNA, Ab/LNP-mRNA is independent of apolipoprotein E. Vascular re-targeting of mRNA represents a promising, powerful, and unique approach for novel experimental and clinical interventions in organs of interest other than liver.
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