PXD050196-1
PXD050196 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Directed Evolution of Genetically Encoded LYTACs for Cell-Mediated Delivery |
| Description | Lysosome-targeting chimeras (LYTACs) are a promising therapeutic modality to drive the degradation of extracellular proteins. However, early versions of LYTAC contain synthetic glycopeptides that cannot be genetically encoded. Here we present our designs for a fully genetically encodable LYTAC (GELYTAC), making our tool compatible with integration into therapeutic cells for targeted delivery at diseased sites. To achieve this, we replaced the glycopeptide portion of LYTACs with the protein insulin like growth factor 2 (IGF2). After showing initial efficacy with wild type IGF2, we increased the potency of GELYTAC using directed evolution. Subsequently, we demonstrated that our engineered GELYTAC construct not only secretes from HEK293T cells but also from human primary T-cells to drive the uptake of various targets into receiver cells. Immune cells engineered to secrete GELYTAC thus represent a promising avenue for spatially-selective targeted protein degradation. |
| HostingRepository | MassIVE |
| AnnounceDate | 2024-03-04 |
| AnnouncementXML | Submission_2024-03-04_07:53:02.033.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | David Roberts |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; scientific name: Escherichia coli; common name: E. coli; NCBI TaxID: 562; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | 6230B Time-of-Flight LC/MS |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2024-02-27 12:13:00 | ID requested | |
| ⏵ 1 | 2024-03-04 07:53:02 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Targeted protein degradation, cell therapy, GELYTAC |
Contact List
| Carolyn Bertozzi | |
|---|---|
| contact affiliation | Stanford University |
| contact email | bertozzi@stanford.edu |
| lab head | |
| David Roberts | |
| contact affiliation | Stanford University |
| contact email | dsroberts@stanford.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/v07/MSV000094184/ |
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