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

242 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

Lipid-like nanoparticles
genetic disorders
hemophilia
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.",

keywords = "Lipid-like nanoparticles, genetic disorders, hemophilia, mRNA delivery, orthogonal array design",

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

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doi = "10.1021/acs.nanolett.5b03528",

language = "English",

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T1 - An Orthogonal Array Optimization of Lipid-like Nanoparticles for mRNA Delivery in Vivo

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 - Lipid-like nanoparticles

KW - genetic disorders

KW - hemophilia

KW - mRNA delivery

KW - orthogonal array design

UR - https://www.scopus.com/pages/publications/84949637138

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DO - 10.1021/acs.nanolett.5b03528

M3 - Article

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AN - SCOPUS:84949637138

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VL - 15

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EP - 8107

JO - Nano Letters

JF - Nano Letters

IS - 12

ER -

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

Abstract

Keywords

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