- Simplifying the Chemical Structure of Cationic Lipids for siRNA-Lipid Nanoparticles
-
We report a potent cationic lipid, SST-02 ((3-hydroxylpropyl)dilinoleylamine), which possesses a simple chemical structure and is synthesized just in one step. Cationic lipids are key components of siRNA-lipid nanoparticles (LNP), which may serve as potential therapeutic agents for various diseases. For a decade, chemists have given enhanced potency and new functions to cationic lipids along with structural complexity. In this study, we conducted a medicinal chemistry campaign pursuing chemical simplicity and found that even dilinoleylmethylamine (SST-01) and methylpalmitoleylamine could be used for the in vitro and in vivo siRNA delivery. Further optimization revealed that a hydroxyl group boosted potency, and SST-02 showed an ID50 of 0.02 mg/kg in the factor VII (FVII) model. Rats administered with 3 mg/kg of SST-02 LNP did not show changes in body weight, blood chemistry, or hematological parameters, while the AST level decreased at a dose of 5 mg/kg. The use of SST-02 avoids a lengthy synthetic route and may thus decrease the future cost of nucleic acid therapeutics.
- Kuboyama, Takeshi,Yagi, Kaori,Naoi, Tomoyuki,Era, Tomohiro,Yagi, Nobuhiro,Nakasato, Yoshisuke,Yabuuchi, Hayato,Takahashi, Saori,Shinohara, Fumikazu,Iwai, Hiroto,Koubara-Yamada, Ayumi,Hasegawa, Kazumasa,Miwa, Atsushi
-
supporting information
p. 749 - 753
(2019/05/06)
-
- Cationic lipid compound and its preparation method
-
The invention discloses cationic lipid compounds and a preparation method thereof. The molecular structure general formula of the compounds is shown as the description, wherein R is alkyl groups of C6 to C24, alkylenes of C6 to C24 and acyl groups of C6 t
- -
-
Paragraph 0025; 0028
(2017/07/11)
-
- LIPID ENCAPSULATING INTERFERING RNA
-
Rich tooling is provided for REST application development that integrates the exploration of a REST API, modeling of data types and the REST API, and the generation of artifacts using the modeled REST API and data types.
- -
-
Paragraph 0249-0251
(2016/05/24)
-
- IMPROVED COMPOSITIONS AND METHODS FOR THE DELIVERY OF NUCLEIC ACIDS
-
The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of specific target protein at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.
- -
-
Paragraph 0210-0211
(2016/08/17)
-
- COMPOSITIONS AND METHODS FOR ENHANCING CELLULAR UPTAKE AND INTRACELLULAR DELIVERY OF LIPID PARTICLES
-
Compositions, methods and compounds useful for enhancing the uptake of a lipid particle b\ a cell are described In particular embodiments, the methods of the invention include contacting a cell with a lipid particle and a compound that binds a Na+/K+ ATPase to enhance uptake of the lipid particle b\ the cell Related compositions useful in practicing methods include lipid particles comprising a conjugated compound that enhances uptake of the lipid particles b\ the cell The methods and compositions are useful in delivering a therapeutic agent to a cell, e g for the treatment of a disease or disorder in a subject
- -
-
Page/Page column 43
(2012/10/23)
-
- IMPROVED AMINO LIPIDS AND METHODS FOR THE DELIVERY OF NUCLEIC ACIDS
-
The present invention provides superior compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of specific target proteins at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.
- -
-
Page/Page column 89-90
(2010/04/28)
-