دورية أكاديمية
Preclinical evaluation of ADVM-062, a novel intravitreal gene therapy vector for the treatment of blue cone monochromacy.
| العنوان: | Preclinical evaluation of ADVM-062, a novel intravitreal gene therapy vector for the treatment of blue cone monochromacy. |
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| المؤلفون: | Hanna K; Adverum Biotechnologies, Inc., Redwood City, CA 94063, USA., Nieves J; Adverum Biotechnologies, Inc., Redwood City, CA 94063, USA., Dowd C; Adverum Biotechnologies, Inc., Redwood City, CA 94063, USA., Bender KO; Adverum Biotechnologies, Inc., Redwood City, CA 94063, USA., Sharma P; Adverum Biotechnologies, Inc., Redwood City, CA 94063, USA., Singh B; Adverum Biotechnologies, Inc., Redwood City, CA 94063, USA., Renz M; Adverum Biotechnologies, Inc., Redwood City, CA 94063, USA., Ver Hoeve JN; Ocular Services on Demand (OSOD), Madison, WI 53719, USA., Cepeda D; Adverum Biotechnologies, Inc., Redwood City, CA 94063, USA., Gelfman CM; Adverum Biotechnologies, Inc., Redwood City, CA 94063, USA., Riley BE; Adverum Biotechnologies, Inc., Redwood City, CA 94063, USA. Electronic address: briley@adverum.com., Grishanin RN; Adverum Biotechnologies, Inc., Redwood City, CA 94063, USA. Electronic address: rgrishanin@adverum.com. |
| المصدر: | Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2023 Jul 05; Vol. 31 (7), pp. 2014-2027. Date of Electronic Publication: 2023 Mar 16. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 100890581 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-0024 (Electronic) Linking ISSN: 15250016 NLM ISO Abbreviation: Mol Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2017- : Cambridge, MA : Cell Press Original Publication: San Diego, CA : Academic Press, 2000- |
| مواضيع طبية MeSH: | Retinal Cone Photoreceptor Cells*/metabolism , Opsins*/genetics, Animals ; Humans ; Primates/genetics ; Primates/metabolism ; Rod Opsins/genetics ; Rod Opsins/metabolism ; Genetic Therapy/methods |
| مستخلص: | Blue cone monochromacy (BCM) is a rare X-linked retinal disease characterized by the absence of L- and M-opsin in cone photoreceptors, considered a potential gene therapy candidate. However, most experimental ocular gene therapies utilize subretinal vector injection which would pose a risk to the fragile central retinal structure of BCM patients. Here we describe the use of ADVM-062, a vector optimized for cone-specific expression of human L-opsin and administered using a single intravitreal (IVT) injection. Pharmacological activity of ADVM-062 was established in gerbils, whose cone-rich retina naturally lacks L-opsin. A single IVT administration dose of ADVM-062 effectively transduced gerbil cone photoreceptors and produced a de novo response to long-wavelength stimuli. To identify potential first-in-human doses we evaluated ADVM-062 in non-human primates. Cone-specific expression of ADVM-062 in primates was confirmed using ADVM-062.myc, a vector engineered with the same regulatory elements as ADVM-062. Enumeration of human OPN1LW.myc-positive cones demonstrated that doses ≥3 × 10 10 vg/eye resulted in transduction of 18%-85% of foveal cones. A Good Laboratory Practice (GLP) toxicology study established that IVT administration of ADVM-062 was well tolerated at doses that could potentially achieve clinically meaningful effect, thus supporting the potential of ADVM-062 as a one-time IVT gene therapy for BCM. Competing Interests: Declaration of interests K.H., D.C., J.N., C.D., P.S., K.O.B., M.R., B.S., C.M.G., B.E.R., and R.N.G. are current or previous employees of Adverum Biotechnologies and hold stock grants. J.V.H. is a paid consultant of Adverum Biotechnologies. (Copyright © 2023 Adverum Biotechnologies Inc. Published by Elsevier Inc. All rights reserved.) |
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| فهرسة مساهمة: | Keywords: AAV; OPN1LW; animal models; blue cone monochromatism; cone photoreceptors; fovea; gene therapy; inherited retinal disorder; intravitreal; non-human primate |
| المشرفين على المادة: | 0 (Opsins) 0 (Rod Opsins) |
| SCR Disease Name: | Blue cone monochromatism |
| تواريخ الأحداث: | Date Created: 20230318 Date Completed: 20230710 Latest Revision: 20240706 |
| رمز التحديث: | 20240706 |
| مُعرف محوري في PubMed: | PMC10362383 |
| DOI: | 10.1016/j.ymthe.2023.03.011 |
| PMID: | 36932675 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1525-0024 |
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| DOI: | 10.1016/j.ymthe.2023.03.011 |