Gene-terapia: ikuspegi terapeutiko berria begietako gaitzen tratamenduan

Abstract

Gene-terapia etorkizun handiko tresna bezala sortu da tratamendurik ez duten asaldurentzat. Azido nukleiko terapeutikoen administrazioan oinarritzen da gaixotasunak tratatzeko. Gene-terapia arrakastatsua izan dadin material genetikoaren askapen eraginkorra bermatu behar da itu-zeluletan. Geneen administrazio-sistemen artean, bektore biralak asko erabili dira ahalbidetzen duten transferentzia genikorako gaitasun onarengatik. Hala ere, horien arrisku nagusien ondorioz (immunogenizitatea eta mutagenesia), bektore ez-biralen diseinua sustatu da. Bektore ez-biralak seguruagoak dira eta ekoizpena errazagoa da, baina hauen muga nagusia transfekzio-eraginkortasun baxua da. Gene-terapiarako organo interesgarri bat begia da, eskuragarria eta aztertzeko erraza baita. Gainera, immunitate-sistematik babestuta dago. Gene-terapia entsegu kliniko guztien % 1,3 bakarrik tratatzen dituzte begietako gaitzak, baina etorkizun handia aurkeztu dute azken urteetan. Izan ere, 2018an Estatu Batuetan eta Europan gene-terapian oinarritutako begirako lehen medikamentuaren komertzializazioa onartu zen, Luxturna®, Sortzetiko Leberren Amaurosiaren tratamendurako. Berrikuspen honetan, begiko administrazio-bideak, gene-terapia estrategiak eta transferentzia geniko eraginkorrerako gainditu behar diren begiko mugak aurkezten dira. Halaber, gene-terapiaren bidez tratatzeko hautagai diren begietako gaitz ezberdinak ere biltzen dira. Gene-terapiaren inguruan egindako ahaleginei eta aurrerapenei esker, begietako gaitzak tratatzeko medikamentu berriak garatu dira. Horietako asko entsegu klinikoetan ebaluatzen ari dira oraindik, baina beste batzuk jada merkatura eta pazienteetara iritsi dira.; Gene therapy has emerged as a promising tool for disorders that have no cure. It consists in the administration of therapeutic nucleic acids into patients for treating diseases. The success of gene therapy relies on the efficient delivery of the genetic material to target cells. Among gene delivery systems, viral vectors have been widely used due to their good gene transference efficacy. However, their potential risk associated with immunogenicity and mutagenesis has promoted the design of non-viral vectors. Non-viral vectors are safer and easier to produce, but their main limitation remains lower transfection efficacy. An attractive candidate for gene therapy is the eye, since it is easily accessible, easily examined and relatively immune privileged. Only 1,3% of all gene therapy clinical trials treat ocular disorders, but they have shown great potential in recent years. In fact, in 2018 the Food and Drug Administration and the European Medicine Agency approved the commercialization of the first gene therapy based ocular drug, Luxturna®, for the treatment of Leber Congenital Amaurosis. In this review, we present the main administration routes to eye, gene therapy strategies and ocular barriers to overcome for successful gene transfer. Different ocular disease candidates to be treated by gene therapy are also reviewed. The efforts and advances made in the field of gene therapy have led to the development of new drugs to treat eye diseases. Many of them are still being evaluated in clinical trials, but some have already reached the market and patients.