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| Status |
Public on Jul 29, 2016 |
| Title |
A multi-functional AAV-CRISPR-Cas9 and its host response |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
CRISPR-Cas9 delivery by AAV holds promise for gene therapy but faces critical barriers due to its potential immunogenicity and limited payload capacity. Here, we demonstrate genome engineering in postnatal mice using AAV-split-Cas9, a multi-functional platform customizable for genome-editing, transcriptional regulation, and other previously impracticable AAV-CRISPR-Cas9 applications. We identify crucial parameters that impact efficacy and clinical translation of our platform, including viral biodistribution, editing efficiencies in various organs, antigenicity, immunological reactions, and physiological outcomes. These results reveal that AAV-CRISPR-Cas9 evokes host responses with distinct cellular and molecular signatures, but unlike alternative delivery methods, does not induce detectable cellular damage in vivo. Our study provides a foundation for developing effective genome therapeutics
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| Overall design |
mRNA-Seq from muscles (9 samples; 3 mice x 3 conditions) and lymph nodes (9 samples; 3 mice x 3 conditions).
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| Contributor(s) |
Chew WL, Ng AH |
| Citation(s) |
27595405 |
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| Submission date |
Jul 18, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Alex Ng |
| Organization name |
Harvard Medical School
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| Department |
Genetics
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| Lab |
Church
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| Street address |
77 Avenue Louis Pasteur Rm 233
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (18)
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| GSM2241596 |
Muscle TurboRFP (control, biological replicate 1) |
| GSM2241597 |
Muscle TurboRFP (control, biological replicate 2) |
| GSM2241598 |
Muscle TurboRFP (control, biological replicate 3) |
| GSM2241599 |
Muscle TurboRFP, AAV9-Cas9-VPR-gRNAs Mstn and Fst (biological replicate 1) |
| GSM2241600 |
Muscle TurboRFP, AAV9-Cas9-VPR-gRNAs Mstn and Fst (biological replicate 2) |
| GSM2241601 |
Muscle TurboRFP, AAV9-Cas9-VPR-gRNAs Mstn and Fst (biological replicate 3) |
| GSM2241602 |
Muscle TurboRFP, AAV9-Cas9-VPR-gRNAs Mstn, Fst, Pd-l1, Cd47 (biological replicate 1) |
| GSM2241603 |
Muscle TurboRFP, AAV9-Cas9-VPR-gRNAs Mstn, Fst, Pd-l1, Cd47 (biological replicate 2) |
| GSM2241604 |
Muscle TurboRFP, AAV9-Cas9-VPR-gRNAs Mstn, Fst, Pd-l1, Cd47 (biological replicate 3) |
| GSM2241605 |
Lymph Nodes TurboRFP (control, biological replicate 1) |
| GSM2241606 |
Lymph Nodes TurboRFP (control, biological replicate 2) |
| GSM2241607 |
Lymph Nodes TurboRFP (control, biological replicate 3) |
| GSM2241608 |
Lymph Nodes TurboRFP, AAV9-Cas9-VPR-gRNAs Mstn and Fst (biological replicate 1) |
| GSM2241609 |
Lymph Nodes TurboRFP, AAV9-Cas9-VPR-gRNAs Mstn and Fst (biological replicate 2) |
| GSM2241610 |
Lymph Nodes TurboRFP, AAV9-Cas9-VPR-gRNAs Mstn and Fst (biological replicate 3) |
| GSM2241611 |
Lymph Nodes TurboRFP, AAV9-Cas9-VPR-gRNAs Mstn, Fst, Pd-l1, Cd47 (biological replicate 1) |
| GSM2241612 |
Lymph Nodes TurboRFP, AAV9-Cas9-VPR-gRNAs Mstn, Fst, Pd-l1, Cd47 (biological replicate 2) |
| GSM2241613 |
Lymph Nodes TurboRFP, AAV9-Cas9-VPR-gRNAs Mstn, Fst, Pd-l1, Cd47 (biological replicate 3) |
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| Relations |
| BioProject |
PRJNA329547 |
| SRA |
SRP078860 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE84534_Chew2016naturemethods-supptable1.xls.gz |
11.5 Mb |
(ftp)(http) |
XLS |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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