{"id":132268,"date":"2025-11-14T03:21:08","date_gmt":"2025-11-14T03:21:08","guid":{"rendered":"https:\/\/www.newsbeep.com\/il\/132268\/"},"modified":"2025-11-14T03:21:08","modified_gmt":"2025-11-14T03:21:08","slug":"extracellular-vesicles-show-promise-for-gene-therapy-alternative","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/il\/132268\/","title":{"rendered":"Extracellular Vesicles Show Promise for Gene Therapy Alternative"},"content":{"rendered":"

\"DoctorCredit: Ivan-balvan\/Getty Images<\/p>\n

Extracellular vesicles (EV) could provide a way of editing genes that does not involve viral vectors, with preclinical studies showing positive results for genetic hearing loss.<\/p>\n

Researchers developed a microfluidic electrotransfection platform called \u03bcDES to efficiently load EVs with gene editing ribonucleoprotein (RNP).<\/p>\n

The microfluidic droplet-based EV electroporation system with continuous flow\u2013based droplet generation and low-voltage electroporation offers high-throughput and scalability while minimizing impact on EV integrity and RNP function.<\/p>\n

Xiaoshu Pan, PhD, from the University of Florida, and colleagues report that the \u03bcDES had ten times the loading capacity and more than 1000 times the processing throughput for loading RNP complexes into EVs compared with conventional transfection methods.<\/p>\n

\u201cThis platform could enable the loading of mutation-specific gene editing machinery into EVs, in turn enabling customization of treatment on the basis of patients\u2019 heterogeneous mutational backgrounds, which holds potential for overcoming some of the current challenges in gene therapy,\u201d they write in Science Translational Medicine<\/a>.<\/p>\n

The EV membrane consists of a lipid bilayer with a similar protein composition as the donor cell, which can be transiently permeabilized by pulsed electric shock.<\/p>\n

Microfluidic droplet\u2013based electroporation fully takes advantage of efficient mass transport in confined space to maximize EV loading capacity, creating optimal gene editing efficiency both in vitro and in vivo.<\/p>\n

Fast continuous flow of droplets prevents direct contact of EVs with electrodes and avoids any thermal damage to EVs to retain their natural integrity and stability.<\/p>\n

In contrast with the high voltages used in conventional workflows, the technology substantially minimizes joule heating and high voltage risk by using only about 30 volts while still maintaining effective loading efficiency.<\/p>\n

The uniform electric field can be precisely controlled in a compact droplet space, which can greatly improve consistency and transfection efficiency.<\/p>\n

In a proof-of-concept study, the team demonstrated the effectiveness of their system using \u03bcDES-produced EVs loaded with sgRNA: Cas9 RNPs to target a mouse model of progressive autosomal dominant hearing loss caused by a mutation in the Myo7a\u00a0gene.<\/p>\n

In humans, MYO7A encodes the unconventional myosin VIIA protein in auditory and vestibular hair cells, which plays an essential role in the development of sensory hair cells and signal transduction.<\/p>\n

Mutations in this gene lead to between 39% to 55% of the cases of the most common form of Usher syndrome, which is linked to profound, congenital deafness.<\/p>\n

It is also linked with autosomal dominant and recessive hearing loss that is not associated with other signs or symptoms, as well as familial age-related hearing loss.<\/p>\n

The team found that \u03bcDES-produced EVs loaded with sgRNA: Cas9 RNP protected against hearing loss in the mice, with low off-target editing and no evidence of ototoxicity according to auditory brainstem response.<\/p>\n

The researchers maintain that these results establish proof of concept for this platform as the basis for delivery of gene editing and potentially other cargos for inner ear\u2013specific applications.<\/p>\n

\u201cGenome editing using Cas9-based gene editing technology is a promising approach to correct genetic defects underlying autosomal dominant hearing loss,\u201d they reported. \u201cEncapsulating sgRNA: Cas9 RNPs in EVs provides a transient way to target the inner ear yet potentially durable approach for precise genome modification in the inner ear.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"Credit: Ivan-balvan\/Getty Images Extracellular vesicles (EV) could provide a way of editing genes that does not involve viral…\n","protected":false},"author":2,"featured_media":132269,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3],"tags":[82632,7994,82633,38798,42,17622,30990,43,3173,7143,82634,40,38,3171,41,39,82635],"class_list":["post-132268","post","type-post","status-publish","format-standard","has-post-thumbnail","category-headlines","tag-extracellular-vesicles","tag-gene-editing","tag-gene-therapy-therapeutics","tag-genetic-diseases","tag-headlines","tag-hearing-loss","tag-microfluidics","tag-news","tag-news-features","tag-precision-medicine","tag-preclinical-development","tag-top-news","tag-top-stories","tag-topics","tag-topnews","tag-topstories","tag-viral-vector-applied-microbiology"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/132268","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/comments?post=132268"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/132268\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media\/132269"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media?parent=132268"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/categories?post=132268"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/tags?post=132268"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}