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| Status |
Public on Sep 14, 2023 |
| Title |
Modular Pooled Discovery of Synthetic Knockin Sequences to Program Durable Cell Therapies [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Chronic stimulation can cause T cell dysfunction and limit efficacy of cellular immunotherapies. CRISPR screens have nominated gene targets for engineered T cells, but improved methods are required to compare large numbers of synthetic knockin sequences to reprogram cell functions. Here, we developed Modular Pooled Knockin Screening (ModPoKI), an adaptable platform for modular construction of DNA knockin libraries using barcoded multicistronic adaptors. We built two ModPoKI libraries of 100 transcription factors (TFs) and 129 natural and synthetic surface receptors. Over 30 ModPoKI screens across human TCR and CAR T cells in diverse conditions identified a transcription factor AP4 (TFAP4) construct that enhanced fitness of chronically-stimulated CAR T cells and anti-cancer function in vitro and in vivo. ModPoKI’s modularity allowed us to generate a ~10,000-member library of TF combinations. Non-viral knockin of a combined BATF-TFAP4 polycistronic construct further enhanced function. ModPoKI facilitates discovery of complex gene constructs to program cellular functions.
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| Overall design |
ChIP-Sequencing with BATF and TFAP4 antibodies using primary human GD2 CAR T cells with BATF, TFAP4, BATF-TFAP4 or control (tNGFR) knockin
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| Contributor(s) |
Blaeschke F, Chen YY, Apathy R, Daniel B, Chen AY, Chen PA, Sandor K, Zhang W, Li Z, Mowery C, Yamamoto TN, Nyberg WA, To A, Yu R, Bueno R, Kim MC, Schmidt R, Goodman DB, Feuchtinger T, Eyquem J, Ye CJ, Carnevale J, Satpathy AT, Shifrut E, Roth TL, Marson A |
| Citation(s) |
37714135 |
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| Submission date |
May 18, 2023 |
| Last update date |
Dec 17, 2023 |
| Contact name |
Franziska Blaeschke |
| Organization name |
Gladstone Institutes
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| Street address |
1650 Owens Street
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94158 |
| Country |
USA |
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| Platforms (1) |
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| Samples (24)
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| GSM7383779 |
T cells, BATF-TFAP4 knockin, TFAP4 antibody, donor 1 |
| GSM7383780 |
T cells, BATF knockin, TFAP4 antibody, donor 1 |
| GSM7383781 |
T cells, TFAP4 knockin, TFAP4 antibody, donor 1 |
| GSM7383782 |
T cells, tNGFR knockin, TFAP4 antibody, donor 1 |
| GSM7383783 |
T cells, BATF-TFAP4 knockin, TFAP4 antibody, donor 2 |
| GSM7383784 |
T cells, BATF knockin, TFAP4 antibody, donor 2 |
| GSM7383785 |
T cells, TFAP4 knockin, TFAP4 antibody, donor 2 |
| GSM7383786 |
T cells, tNGFR knockin, TFAP4 antibody, donor 2 |
| GSM7383787 |
T cells, BATF-TFAP4 knockin, TFAP4 antibody, donor 3 |
| GSM7383788 |
T cells, BATF knockin, TFAP4 antibody, donor 3 |
| GSM7383789 |
T cells, TFAP4 knockin, TFAP4 antibody, donor 3 |
| GSM7383790 |
T cells, tNGFR knockin, TFAP4 antibody, donor 3 |
| GSM7383791 |
T cells, BATF-TFAP4 knockin, BATF antibody, donor 1 |
| GSM7383792 |
T cells, BATF knockin, BATF antibody, donor 1 |
| GSM7383793 |
T cells, TFAP4 knockin, BATF antibody, donor 1 |
| GSM7383794 |
T cells, tNGFR knockin, BATF antibody, donor 1 |
| GSM7383795 |
T cells, BATF-TFAP4 knockin, BATF antibody, donor 2 |
| GSM7383796 |
T cells, BATF knockin, BATF antibody, donor 2 |
| GSM7383797 |
T cells, TFAP4 knockin, BATF antibody, donor 2 |
| GSM7383798 |
T cells, tNGFR knockin, BATF antibody, donor 2 |
| GSM7383799 |
T cells, BATF-TFAP4 knockin, BATF antibody, donor 3 |
| GSM7383800 |
T cells, BATF knockin, BATF antibody, donor 3 |
| GSM7383801 |
T cells, TFAP4 knockin, BATF antibody, donor 3 |
| GSM7383802 |
T cells, tNGFR knockin, BATF antibody, donor 3 |
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| This SubSeries is part of SuperSeries: |
| GSE232824 |
Modular Pooled Discovery of Synthetic Knockin Sequences to Program Durable Cell Therapies |
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| Relations |
| BioProject |
PRJNA974026 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE232816_dds.chip.batf2.rds.gz |
2.7 Mb |
(ftp)(http) |
RDS |
| GSE232816_dds.chip.tfap4.2.rds.gz |
35.2 Mb |
(ftp)(http) |
RDS |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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