Functionalized lipid-like nanoparticles for in vivo mRNA delivery and base editing

被引：135

作者：

Zhang, Xinfu ^{[1
,2
]}

Zhao, Weiyu ^{[1
]}

Nguyen, Giang N. ^{[3
]}

Zhang, Chengxiang ^{[1
]}

Zeng, Chunxi ^{[1
]}

Yan, Jingyue ^{[1
]}

Du, Shi ^{[1
]}

Hou, Xucheng ^{[1
]}

Li, Wenqing ^{[1
]}

Jiang, Justin ^{[1
]}

Deng, Binbin ^{[4
]}

McComb, David W. ^{[4
,5
]}

Dorkin, Robert ^{[6
]}

Shah, Aalok ^{[6
]}

Barrera, Luis ^{[6
]}

Gregoire, Francine ^{[6
]}

Singh, Manmohan ^{[6
]}

Chen, Delai ^{[6
]}

Sabatino, Denise E. ^{[3
,7
]}

Dong, Yizhou ^{[1
,8
,9
,10
,11
,12
]}

机构：

[1] Ohio State Univ, Coll Pharm, Div Pharmaceut & Pharmacol, Columbus, OH 43210 USA

[2] Dalian Univ Technol, State Key Lab Fine Chem, Dalian 116024, Peoples R China

[3] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA

[4] Ohio State Univ, Ctr Electron Microscopy & Anal, Dept Mat Sci & Engn, Columbus, OH 43210 USA

[5] Ohio State Univ, Dept Mat Sci & Engn, Columbus, OH 43210 USA

[6] Beam Therapeut, Cambridge, MA 02139 USA

[7] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[8] Ohio State Univ, Dept Biomed Engn, Columbus, OH 43210 USA

[9] Ohio State Univ, Ctr Clin & Translat Sci, Columbus, OH 43210 USA

[10] Ohio State Univ, Comprehensive Canc Ctr, Columbus, OH 43210 USA

[11] Ohio State Univ, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USA

[12] Ohio State Univ, Dept Radiat Oncol, Columbus, OH 43210 USA

来源：

SCIENCE ADVANCES | 2020年 / 6卷 / 34期

关键词：

FACTOR-VIII; OPTIMIZATION; THERAPY; SYSTEM; DNA;

D O I：

10.1126/sciadv.abc2315

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Messenger RNA (mRNA) therapeutics have been explored to treat various genetic disorders. Lipid-derived nanomaterials are currently one of the most promising biomaterials that mediate effective mRNA delivery. However, efficiency and safety of this nanomaterial-based mRNA delivery remains a challenge for clinical applications. Here, we constructed a series of lipid-like nanomaterials (LLNs), named functionalized TT derivatives (FTT), for mRNA-based therapeutic applications in vivo. After screenings on the materials, we identified FTT5 as a lead material for efficient delivery of long mRNAs, such as human factor VIII (hFVIII) mRNA (similar to 4.5 kb) for expression of hFVIII protein in hemophilia A mice. Moreover, FTT5 LLNs demonstrated high percentage of base editing on PCSK9 in vivo at a low dose of base editor mRNA (similar to 5.5 kb) and single guide RNA. Consequently, FTT nanomaterials merit further development for mRNA-based therapy.

引用

页数：8

共 50 条

[41] Synergistic Silencing: Combinations of Lipid-like Materials for Efficacious siRNA Delivery
Whitehead, Kathryn A.
Sahay, Gaurav
Li, George Z.
Love, Kevin T.
Alabi, Christopher A.
Ma, Minglin
Zurenko, Christopher
Querbes, William
Langer, Robert S.
Anderson, Daniel G.
MOLECULAR THERAPY, 2011, 19 (09) : 1688 - 1694
[42] Spatial Resolution of mRNA Lipid Nanoparticle-Based In Vivo Base Editing in the Liver of Mice and Monkeys
Chamberlain, Thomas
Janjuha, Sharan
Haenggi, Tatjana
Marquart, Kim
Eisenhardt, Merete
Semple, Sean C.
Schwank, Gerald
Tam, Ying
MOLECULAR THERAPY, 2024, 32 (04) : 592 - 592
[43] In vivo base editing of Angptl3 via lipid nanoparticles to treat cardiovascular disease
Khirallah, Jennifer
Bloomer, Hanan
Wich, Douglas
Huang, Changfeng
Workman, J. Noah
Li, Yamin
Newby, Gregory A.
Liu, David R.
Xu, Qiaobing
MOLECULAR THERAPY NUCLEIC ACIDS, 2025, 36 (02):
[44] Cationic Lipid Pairs Enhance Liver-to-Lung Tropism of Lipid Nanoparticles for In Vivo mRNA Delivery
Zeng, Gege
He, Zepeng
Yang, Haihong
Gao, Zhan
Ge, Xueer
Liu, Lixin
Liu, Zhijia
Chen, Yongming
ACS APPLIED MATERIALS & INTERFACES, 2024, 16 (20) : 25698 - 25709
[45] A Potent Branched-Tail Lipid Nanoparticle Enables Multiplexed mRNA Delivery and Gene Editing In Vivo
Hajj, Khalid A.
Melamed, Jilian R.
Chaudhary, Namit
Lamson, Nicholas G.
Ball, Rebecca L.
Yerneni, Saigopalakrishna S.
Whitehead, Kathryn A.
NANO LETTERS, 2020, 20 (07) : 5167 - 5175
[46] EGFR-targeted ionizable lipid nanoparticles enhance in vivo mRNA delivery to the placenta
Geisler, Hannah C.
Ghalsasi, Aditi A.
Safford, Hannah C.
Swingle, Kelsey L.
Thatte, Ajay S.
Mukalel, Alvin J.
Gong, Ningqiang
Hamilton, Alex G.
Han, Emily L.
Nachod, Benjamin E.
Padilla, Marshall S.
Mitchell, Michael J.
JOURNAL OF CONTROLLED RELEASE, 2024, 371 : 455 - 469
[47] SPECIFIC IN VIVO DELIVERY OF PROCOLLAGEN α1(I) siRNA IN LIPID-LIKE CARRIERS INHIBITS THE PROGRESSION OF BILIARY LIVER FIBROSIS
Calvente, C.
Diken, M.
Sehgal, A.
Kim, Y. O.
Schuppan, D.
JOURNAL OF HEPATOLOGY, 2013, 58 : S236 - S236
[48] Functionalized solid lipid nanoparticles for transendothelial delivery
Jayagopal, Ashwath
Sussman, Eric A.
Shastri, Venkatram Prasad
IEEE TRANSACTIONS ON NANOBIOSCIENCE, 2008, 7 (01) : 28 - 34
[49] Effects of local structural transformation of lipid-like compounds on delivery of messenger RNA
Bin Li
Xiao Luo
Binbin Deng
JoLynn B. Giancola
David W. McComb
Thomas D. Schmittgen
Yizhou Dong
Scientific Reports, 6
[50] Recent advances in lipid nanoparticles for delivery of nucleic acid, mRNA, and gene editing-based therapeutics
Mukai, Hidefumi
Ogawa, Koki
Kato, Naoya
Kawakami, Shigeru
DRUG METABOLISM AND PHARMACOKINETICS, 2022, 44

← 1 2 3 4 5 →