دورية أكاديمية
mRNA-based therapy proves superior to the standard of care for treating hereditary tyrosinemia 1 in a mouse model
| العنوان: | mRNA-based therapy proves superior to the standard of care for treating hereditary tyrosinemia 1 in a mouse model |
|---|---|
| المؤلفون: | Maximiliano L. Cacicedo, Christine Weinl-Tenbruck, Daniel Frank, Sebastian Wirsching, Beate K. Straub, Jana Hauke, Jürgen G. Okun, Nigel Horscroft, Julia B. Hennermann, Fred Zepp, Frédéric Chevessier-Tünnesen, Stephan Gehring |
| المصدر: | Molecular Therapy: Methods & Clinical Development, Vol 26, Iss , Pp 294-308 (2022) |
| بيانات النشر: | Elsevier, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Genetics LCC:Cytology |
| مصطلحات موضوعية: | hereditary tyrosinemia type 1, fumarylacetoacetate hydrolase, nitisinone supplementation, mRNA-based therapy, mouse model, Genetics, QH426-470, Cytology, QH573-671 |
| الوصف: | Hereditary tyrosinemia type 1 is an inborn error of amino acid metabolism characterized by deficiency of fumarylacetoacetate hydrolase (FAH). Only limited treatment options (e.g., oral nitisinone) are available. Patients must adhere to a strict diet and face a life-long risk of complications, including liver cancer and progressive neurocognitive decline. There is a tremendous need for innovative therapies that standardize metabolite levels and promise normal development. Here, we describe an mRNA-based therapeutic approach that rescues Fah-deficient mice, a well-established tyrosinemia model. Repeated intravenous or intramuscular administration of lipid nanoparticle-formulated human FAH mRNA resulted in FAH protein synthesis in deficient mouse livers, stabilized body weight, normalized pathologic increases in metabolites after nitisinone withdrawal, and prevented early death. Dose reduction and extended injection intervals proved therapeutically effective. These results provide proof of concept for an mRNA-based therapeutic approach to treating hereditary tyrosinemia type 1 that is superior to the standard of care. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2329-0501 55891683 |
| العلاقة: | http://www.sciencedirect.com/science/article/pii/S2329050122000985Test; https://doaj.org/toc/2329-0501Test |
| DOI: | 10.1016/j.omtm.2022.07.006 |
| الوصول الحر: | https://doaj.org/article/c558916830de456c8e082c476d56542cTest |
| رقم الانضمام: | edsdoj.558916830de456c8e082c476d56542c |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 23290501 55891683 |
|---|---|
| DOI: | 10.1016/j.omtm.2022.07.006 |