Safety of Human USH1C Transgene Expression Following Subretinal Injection in Wild-Type Pigs

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F25%3A00605629" target="_blank" >RIV/67985904:_____/25:00605629 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/25:10502652

Result on the web

<a href="https://iovs.arvojournals.org/article.aspx?articleid=2802489" target="_blank" >https://iovs.arvojournals.org/article.aspx?articleid=2802489</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1167/iovs.66.1.48" target="_blank" >10.1167/iovs.66.1.48</a>

Result language

angličtina

Original language name

Safety of Human USH1C Transgene Expression Following Subretinal Injection in Wild-Type Pigs

Original language description

PURPOSE . This study aimed to evaluate early-phase safety of subretinal application of AAVanc80.CAG.USH1Ca1 (OT_USH_101) in wild-type (WT) pigs, examining the effects of a vehicle control, low dose, and high dose. METHODS . Twelve WT pigs (24 eyes) were divided into three groups: four pigs each received bilateral subretinal injections of either vehicle, low dose (3.3 x 1010 vector genomes [vg] per eye), or high dose (1.0 x 1011 vg per eye). Total retinal thickness (TRT) was evaluated using optical coherence tomography and retinal function was assessed with full-field electroretinography (ff-ERG) at baseline and two months post-surgery. After necropsy, retinal changes were examined through histopathology, and human USH1C_a1 /harmonin expression was assessed by quantitative PCR (qPCR) and Western blotting. RESULTS . OT_USH_101 led to high USH1C_a1 expression in WT pig retinas without significant TRT changes two months after subretinal injection. The qPCR revealed expression of the human USH1C_a1 transgene delivered by the adeno-associated virus vector. TRT changes were minimal across groups: vehicle (256 +/- 21 to 243 +/- 18 mu m, P = 0.108), low dose (251 +/- 32 to 258 +/- 30 mu m, P = 0.076), and high dose (242 +/- 24 to 259 +/- 28 mu m, P = 0.590). The ff-ERG showed no significant changes in rod or cone responses. Histopathology indicated no severe retinal adverse effects in the vehicle and low dose groups. CONCLUSIONS . Early-phase clinical imaging, electrophysiology, and histopathological assessments indicated that subretinal administration of OT_USH_101 was well tolerated in the low-dose treatment arm. OT_USH_101 treatment resulted in high expression of human USH1C_a1. Although histopathological changes were not severe, more frequent changes were observed in the high-dose group.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30402 - Technologies involving the manipulation of cells, tissues, organs or the whole organism (assisted reproduction)

Project

<a href="/en/project/EH22_008%2F0004562" target="_blank" >EH22_008/0004562: Excellent Research in Regenerative Medicine</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Investigative Ophthalmology and Visual Science

ISSN

0146-0404

e-ISSN

1552-5783

Volume of the periodical

66

Issue of the periodical within the volume

1

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

48

UT code for WoS article

001405989400014

EID of the result in the Scopus database

2-s2.0-85216439217