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| 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
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| 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.
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| 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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| Web link |
https://github.com/alimagalieva/AIPL1_RNAseq_analysis
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| Contributor(s) |
Galieva A, Egorov A, Malogolovkin A, Brovin A, Karabelsky A |
| Citation(s) |
38203368 |
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| Submission date |
Dec 29, 2023 |
| Last update date |
Jan 25, 2024 |
| Contact name |
Alima Galieva |
| E-mail(s) |
alima.galieva@gmail.com
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| Organization name |
Sirius University of Science and Technology
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| Department |
Gene therapy department
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| Street address |
Olympic Ave, 1
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| City |
Sochi |
| State/province |
Krasnodar region |
| ZIP/Postal code |
354340 |
| Country |
Russia |
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| Platforms (1) |
| GPL18460 |
Illumina HiSeq 1500 (Homo sapiens) |
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| Samples (12)
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| GSM7998495 |
ARPE-19, AAV9-AIPL1co, rep.3 |
| GSM7998496 |
ARPE-19, non-transduced control, rep.1 |
| GSM7998497 |
ARPE-19, AAV9-GFP, rep.1 |
| GSM7998498 |
ARPE-19, AAV9-GFP, rep.3 |
| GSM7998499 |
ARPE-19, AAV9-AIPL1wt, rep.2 |
| GSM7998500 |
ARPE-19, AAV9-AIPL1co, rep.1 |
| GSM7998501 |
ARPE-19, non-transduced control, rep.2 |
| GSM7998502 |
ARPE-19, non-transduced control, rep.3 |
| GSM7998503 |
ARPE-19, AAV9-GFP, rep.2 |
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| Relations |
| BioProject |
PRJNA1059046 |
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