Generation and validation of a Leber Congenital Amaurosis, Type 12 patient-specific iPSC line (LVPEIi006-B) with a splice-site mutation in RD3 and an isogenic mutation-corrected iPSC line (LVPEIi006-B-1)

Leber congenital amaurosis, Type 12 is an early onset, autosomal recessive retinal disease caused by mutations in RD3. We report the generation of a patient-specific iPSC line (LVPEIi006-B), using Sendai viral vector-based reprogramming approach and an isogenic, mutation-corrected iPSC line (LVPEIi0...

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Main Authors: Sudipta Mahato, Savitri Maddileti, Trupti Agrawal, Sundaram Acharya, Chitra Kannabiran, Subhadra Jalali, Debojyoti Chakraborty, Indumathi Mariappan
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Stem Cell Research
Online Access:http://www.sciencedirect.com/science/article/pii/S1873506125000534
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author Sudipta Mahato
Savitri Maddileti
Trupti Agrawal
Sundaram Acharya
Chitra Kannabiran
Subhadra Jalali
Debojyoti Chakraborty
Indumathi Mariappan
author_facet Sudipta Mahato
Savitri Maddileti
Trupti Agrawal
Sundaram Acharya
Chitra Kannabiran
Subhadra Jalali
Debojyoti Chakraborty
Indumathi Mariappan
author_sort Sudipta Mahato
collection DOAJ
description Leber congenital amaurosis, Type 12 is an early onset, autosomal recessive retinal disease caused by mutations in RD3. We report the generation of a patient-specific iPSC line (LVPEIi006-B), using Sendai viral vector-based reprogramming approach and an isogenic, mutation-corrected iPSC line (LVPEIi006-B-1), using an en31FnCas9-based adenine base editor (ABE) system. Both lines were clonally expanded and genotyped to confirm the presence of patient-specific mutation and desired base correction in the edited line. Both lines maintained their stemness, pluripotency, genomic integrity and could differentiate into retinal organoids. The mutation-corrected, heterozygous iPSC-derived retinal organoids displayed a partial restoration of normal RD3 mRNA splicing.
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publisher Elsevier
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series Stem Cell Research
spelling doaj-art-6fa4bd828d684441b9fba35b7b9fe4d12025-08-20T02:18:24ZengElsevierStem Cell Research1873-50612025-06-018510370310.1016/j.scr.2025.103703Generation and validation of a Leber Congenital Amaurosis, Type 12 patient-specific iPSC line (LVPEIi006-B) with a splice-site mutation in RD3 and an isogenic mutation-corrected iPSC line (LVPEIi006-B-1)Sudipta Mahato0Savitri Maddileti1Trupti Agrawal2Sundaram Acharya3Chitra Kannabiran4Subhadra Jalali5Debojyoti Chakraborty6Indumathi Mariappan7Centre for Ocular Regeneration, Prof. Brien Holden Eye Research Centre, Hyderabad Eye Research Foundation, L.V. Prasad Eye Institute, Hyderabad, Telangana, India; Manipal Academy of Higher Education, Manipal, Karnataka, IndiaCentre for Ocular Regeneration, Prof. Brien Holden Eye Research Centre, Hyderabad Eye Research Foundation, L.V. Prasad Eye Institute, Hyderabad, Telangana, IndiaCentre for Ocular Regeneration, Prof. Brien Holden Eye Research Centre, Hyderabad Eye Research Foundation, L.V. Prasad Eye Institute, Hyderabad, Telangana, India; Manipal Academy of Higher Education, Manipal, Karnataka, IndiaCSIR-Institute of Genomics & Integrative Biology, Mathura Road, New Delhi 110025, India; Academy of Scientific & Innovative Research (AcSIR), Ghaziabad 201002, IndiaKallam Anji Reddy Molecular Genetics Laboratory, Prof. Brien Holden Eye Research Centre, Hyderabad Eye Research Foundation, LV Prasad Eye Institute, Hyderabad, Telangana, IndiaSrimati Kanuri Santhamma Centre for Vitreo Retinal Diseases, Anant Bajaj Retina Institute, L.V. Prasad Eye Institute, Hyderabad, Telangana, IndiaCSIR-Institute of Genomics & Integrative Biology, Mathura Road, New Delhi 110025, IndiaCentre for Ocular Regeneration, Prof. Brien Holden Eye Research Centre, Hyderabad Eye Research Foundation, L.V. Prasad Eye Institute, Hyderabad, Telangana, India; Corresponding author at: Centre for Ocular Regeneration, Prof. Brien Holden Eye Research Centre, Hyderabad Eye Research Foundation, LV Prasad Eye Institute, Road No. 2, Banjara Hills, Hyderabad 500034, India.Leber congenital amaurosis, Type 12 is an early onset, autosomal recessive retinal disease caused by mutations in RD3. We report the generation of a patient-specific iPSC line (LVPEIi006-B), using Sendai viral vector-based reprogramming approach and an isogenic, mutation-corrected iPSC line (LVPEIi006-B-1), using an en31FnCas9-based adenine base editor (ABE) system. Both lines were clonally expanded and genotyped to confirm the presence of patient-specific mutation and desired base correction in the edited line. Both lines maintained their stemness, pluripotency, genomic integrity and could differentiate into retinal organoids. The mutation-corrected, heterozygous iPSC-derived retinal organoids displayed a partial restoration of normal RD3 mRNA splicing.http://www.sciencedirect.com/science/article/pii/S1873506125000534
spellingShingle Sudipta Mahato
Savitri Maddileti
Trupti Agrawal
Sundaram Acharya
Chitra Kannabiran
Subhadra Jalali
Debojyoti Chakraborty
Indumathi Mariappan
Generation and validation of a Leber Congenital Amaurosis, Type 12 patient-specific iPSC line (LVPEIi006-B) with a splice-site mutation in RD3 and an isogenic mutation-corrected iPSC line (LVPEIi006-B-1)
Stem Cell Research
title Generation and validation of a Leber Congenital Amaurosis, Type 12 patient-specific iPSC line (LVPEIi006-B) with a splice-site mutation in RD3 and an isogenic mutation-corrected iPSC line (LVPEIi006-B-1)
title_full Generation and validation of a Leber Congenital Amaurosis, Type 12 patient-specific iPSC line (LVPEIi006-B) with a splice-site mutation in RD3 and an isogenic mutation-corrected iPSC line (LVPEIi006-B-1)
title_fullStr Generation and validation of a Leber Congenital Amaurosis, Type 12 patient-specific iPSC line (LVPEIi006-B) with a splice-site mutation in RD3 and an isogenic mutation-corrected iPSC line (LVPEIi006-B-1)
title_full_unstemmed Generation and validation of a Leber Congenital Amaurosis, Type 12 patient-specific iPSC line (LVPEIi006-B) with a splice-site mutation in RD3 and an isogenic mutation-corrected iPSC line (LVPEIi006-B-1)
title_short Generation and validation of a Leber Congenital Amaurosis, Type 12 patient-specific iPSC line (LVPEIi006-B) with a splice-site mutation in RD3 and an isogenic mutation-corrected iPSC line (LVPEIi006-B-1)
title_sort generation and validation of a leber congenital amaurosis type 12 patient specific ipsc line lvpeii006 b with a splice site mutation in rd3 and an isogenic mutation corrected ipsc line lvpeii006 b 1
url http://www.sciencedirect.com/science/article/pii/S1873506125000534
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