Small extracellular vesicles expressing dominant inactivated AMPK [alpha] 1 mutants for treatment of obesity

• Main Authors: LOPEZ PEREZ MARCO ANTONIO, ANDREAZI TOHENA RAFFAELE, MARTINEZ MARTINEZ MARIA DEL CARMEN, MILBANK ERIC
• Format: Patent
• Language: Chinese; English
• Published: 24.05.2024
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; VINEGAR; WINE

The present invention relates to a population of small extracellular vesicles (sEV) for use in the treatment of obesity in a subject in need thereof wherein the sEV population comprises at least one polynucleotide encoding a D168A dominant inactivating AMP-activated protein kinase alpha 1 (AMPK alpha 1-DN) mutant protein operably linked and under the control of a steroid producing factor 1 (SF1) promoter, wherein the sEV is engineered to transiently express in its outer membrane at least one fusion protein comprising a neurotrophic rabies virus (RVG) peptide fused to lysosomal associated membrane protein 2b. The populations are highly safe and effective as the sEV, when administered systemically, is able to function in SF1-expressing neurons located in the medial nucleus of the hypothalamic abdomen. 本发明涉及用于在有需要的对象中治疗肥胖的小胞外囊泡(sEV)群体，其中sEV群体包含至少一种编码可操作地连接并在类固醇生成因子1(SF1)启动子的控制下的D168A显性失活AMP激活蛋白激酶α1(AMPKα1-DN)突变体蛋白的多核苷酸，其中sEV被工程改造以在其外膜中瞬时表达至少一种包含与溶酶体相关膜蛋白2b融合的神经营养性狂犬病病毒(RVG)肽的融合蛋白。所述群体是高度安全和有效的，因为当全身施用时，sEV能够在位于下