КНОПОВ Виктор (US),ВИТТЕ Ричард П. (US),КАРМАЛИ Прия (US),ЛИ Робин (US),ВЕББ Дэвид (US),АКОПЯН Виолетта (US)
申请号：
RU2014122432/15
公开号：
RU2014122432A
申请日:
2012.11.02
申请国别(地区):
RU
年份:
2015
代理人:
摘要：
1. A method of producing a lipid nanoparticle encapsulating a two-filament RNA molecule, comprising the steps of: obtaining a lipid solution containing a cationic lipid, a neutral lipid, sterol and PEG lipid dissolved in a water-miscible organic solvent； obtaining a first aqueous solution containing a concentration of RNA molecule from 0.08 to 0.8 mg / m and an aqueous buffer at pH 4-6； pumping the lipid solution through the tube into the aqueous solution at a constant speed for 1-100 min so that the lipid solution is mixed with the aqueous solution； teaching a mixture containing 25-45% (vol: vol) of an organic solvent and a lipid nanoparticle having an RNA: lipid ratio of from 0.06 to 0.16 (wt: wt.) and an RNA: lipid charge ratio of from 2.5: 1 to 1: one； and removing the organic solvent from the mixture by diafiltration relative to the second aqueous buffered solution at pH 6-8.2. The method of claim 1, wherein the second solution further comprises a polysaccharide. 3. The method of claim 2, wherein the polysaccharide is selected from the group consisting of sucrose, trehalose, lactose, maltose, and inulin. The method of claim 1, further comprising the step of lyophilizing a lipid nanoparticle encapsulating an RNA molecule. The method of claim 1, wherein the organic solution is ethanol. 6. The method of claim 1, wherein the cationic lipid is from 40 to 60 mol% of the lipids. The method of claim 1, wherein the cationic lipid is selected from the group consisting of HEDC, HEDODC and HE-Et-DODC: and 8. The method of claim 1, wherein the cationic lipid consists of an ionizable or non-ionizable positive charge. The method of claim 1, wherein the lipids further comprise a compound containing a retinoid molecule. The method of claim 1, wherein the first solution and the second solution1. Способ получения липидной наночастицы, инкапсулирующей двухнитиевую молекулу РНК, содержащий стадии:получения липидного раствора, содержащего катионный липид, нейтральный липид, стерол и
