An Orthogonal Array Optimization of Lipid-like Nanoparticles for mRNA Delivery in Vivo

Bin Li; Xiao Luo; Binbin Deng; Junfeng Wang; David W. McComb; Yimin Shi; Karin M.L. Gaensler; Xu Tan; Amy L. Dunn; Bryce A. Kerlin; Yizhou Dong

doi:10.1021/acs.nanolett.5b03528

An Orthogonal Array Optimization of Lipid-like Nanoparticles for mRNA Delivery in Vivo

Bin Li, Xiao Luo, Binbin Deng, Junfeng Wang, David W. McComb, Yimin Shi, Karin M.L. Gaensler, Xu Tan, Amy L. Dunn, Bryce A. Kerlin, Yizhou Dong

Research output: Contribution to journal › Article › peer-review

201 Scopus citations

Abstract

Systemic delivery of mRNA-based therapeutics remains a challenging issue for preclinical and clinical studies. Here, we describe new lipid-like nanoparticles (TT-LLNs) developed through an orthogonal array design, which demonstrates improved delivery efficiency of mRNA encoding luciferase in vitro by over 350-fold with significantly reduced experimental workload. One optimized TT3 LLN, termed O-TT3 LLNs, was able to restore the human factor IX (hFIX) level to normal physiological values in FIX-knockout mice. Consequently, these mRNA based nanomaterials merit further development for therapeutic applications.

Original language	English
Pages (from-to)	8099-8107
Number of pages	9
Journal	Nano Letters
Volume	15
Issue number	12
DOIs	https://doi.org/10.1021/acs.nanolett.5b03528
State	Published - 9 Dec 2015
Externally published	Yes

Keywords

genetic disorders
hemophilia
Lipid-like nanoparticles
mRNA delivery
orthogonal array design

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10.1021/acs.nanolett.5b03528

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title = "An Orthogonal Array Optimization of Lipid-like Nanoparticles for mRNA Delivery in Vivo",

abstract = "Systemic delivery of mRNA-based therapeutics remains a challenging issue for preclinical and clinical studies. Here, we describe new lipid-like nanoparticles (TT-LLNs) developed through an orthogonal array design, which demonstrates improved delivery efficiency of mRNA encoding luciferase in vitro by over 350-fold with significantly reduced experimental workload. One optimized TT3 LLN, termed O-TT3 LLNs, was able to restore the human factor IX (hFIX) level to normal physiological values in FIX-knockout mice. Consequently, these mRNA based nanomaterials merit further development for therapeutic applications.",

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AU - Li, Bin

AU - Luo, Xiao

AU - Deng, Binbin

AU - Wang, Junfeng

AU - McComb, David W.

AU - Shi, Yimin

AU - Gaensler, Karin M.L.

AU - Tan, Xu

AU - Dunn, Amy L.

AU - Kerlin, Bryce A.

AU - Dong, Yizhou

PY - 2015/12/9

Y1 - 2015/12/9

N2 - Systemic delivery of mRNA-based therapeutics remains a challenging issue for preclinical and clinical studies. Here, we describe new lipid-like nanoparticles (TT-LLNs) developed through an orthogonal array design, which demonstrates improved delivery efficiency of mRNA encoding luciferase in vitro by over 350-fold with significantly reduced experimental workload. One optimized TT3 LLN, termed O-TT3 LLNs, was able to restore the human factor IX (hFIX) level to normal physiological values in FIX-knockout mice. Consequently, these mRNA based nanomaterials merit further development for therapeutic applications.

AB - Systemic delivery of mRNA-based therapeutics remains a challenging issue for preclinical and clinical studies. Here, we describe new lipid-like nanoparticles (TT-LLNs) developed through an orthogonal array design, which demonstrates improved delivery efficiency of mRNA encoding luciferase in vitro by over 350-fold with significantly reduced experimental workload. One optimized TT3 LLN, termed O-TT3 LLNs, was able to restore the human factor IX (hFIX) level to normal physiological values in FIX-knockout mice. Consequently, these mRNA based nanomaterials merit further development for therapeutic applications.

KW - genetic disorders

KW - hemophilia

KW - Lipid-like nanoparticles

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An Orthogonal Array Optimization of Lipid-like Nanoparticles for mRNA Delivery in Vivo

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Keywords

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