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Series GSE252276 Query DataSets for GSE252276
Status Public on Jan 01, 2024
Title RNA-seq analysis of trans-differentiated ARPE-19 cells transduced by AAV9-AIPL1 vectors
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Inherited retinal disorders (IRD) have become a primary focus of gene therapy research since the success of AAV-based therapeutics (voretigene neparvovec-rzyl) for Leber congenital amaurosis type 2 (LCA2). Dozens of monogenic IRDs could be potentially treated with a similar approach using adeno-associated virus (AAV) to transfer a functional gene into the retina. Here, we present the results of design, production and in vitro testing of the AAV serotype 9 (AAV9) vector carrying the codon-optimized (co) copy of aryl hydrocarbon receptor interacting protein like-1 (AIPL1) as a possible treatment for LCA4. The pAAV-AIPL1co was able to successfully transduce retinal pigment epithelium cells (ARPE-19) and initiate expression of human AIPL1. Intriguingly, cells transduced with AAV9-AIPL1co showed much less antiviral response than AAV9-AIPL1wt (wild type AIPL1 ) transduced. RNA-sequencing (RNA-seq) analysis of trans-differentiated ARPE-19 cells transduced with AAV9-AIPL1co demonstrated the significant differences in expression of genes involved in innate immune response. In contrast, AAV9-AIPL1wt induced prominent activation of multiple interferon-stimulated genes. The key part of possible regulatory molecular mechanism is activation of dsRNA-responsive antiviral oligoadenylate synthetases, and significant increase in level of histone coding genes’ transcripts overrepresented in RNA-seq data (i.e. H1, H2A, H2B, H3 and H4). The RNA-seq data suggests that AAV9-AIPL1co exhibiting less immunogenicity than AAV9-AIPL1wt can be used for potency testing using relevant animal models to develop future therapeutics for LCA4.
Overall design ARPE-19 cells were transduced with AAV9-AIPL1wt, AAV9-AIPL1co or AAV9-GFP (control) vectors. RNA-sequencing of these samples and of non-transduced cells was performed, 3 replicates for each condition
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Contributor(s) Galieva A, Egorov A, Malogolovkin A, Brovin A, Karabelsky A
Citation(s) 38203368
Submission date Dec 29, 2023
Last update date Jan 25, 2024
Contact name Alima Galieva
Organization name Sirius University of Science and Technology
Department Gene therapy department
Street address Olympic Ave, 1
City Sochi
State/province Krasnodar region
ZIP/Postal code 354340
Country Russia
Platforms (1)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
Samples (12)
GSM7998492 ARPE-19, AAV9-AIPL1wt, rep.1
GSM7998493 ARPE-19, AAV9-AIPL1wt, rep.3
GSM7998494 ARPE-19, AAV9-AIPL1co, rep.2
BioProject PRJNA1059046

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Supplementary file Size Download File type/resource
GSE252276_RAW.tar 4.3 Mb (http)(custom) TAR (of TAB)
GSE252276_counts.txt.gz 855.8 Kb (ftp)(http) TXT
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Raw data are available in SRA

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