⮝ Full datasets listing
PXD066528
PXD066528 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Dual AAV gene therapy using laminin-linking proteins ameliorates muscle and nerve defects in LAMA2-related muscular dystrophy |
| Description | Adeno-associated virus (AAV)-mediated gene replacement holds promise for treating genetic diseases but faces challenges due to AAVs limited packaging capacity and potential immune responses to transgene products - particularly in cross-reactive immunologic material (CRIM) - negative patients. LAMA2-related muscular dystrophy (LAMA2 MD), a severe congenital disorder caused by loss of laminin-a2, presents both hurdles: the LAMA2 gene exceeds AAV capacity, and severely affected patients lack endogenous protein, increasing immunogenicity risk. Here, we developed an AAV-based therapy using two engineered linker proteins derived from endogenously expressed components. These linkers restore laminin receptor binding and polymerization, enabling reassembly of a functional basement membrane. Dual AAV delivery of the linkers in a severe LAMA2 MD mouse model resulted in robust expression and significant improvements in muscle histology and function. Using myotropic capsids allowed for efficacy at reduced vector doses. However, muscle-only targeting unmasked LAMA2-related peripheral neuropathy. To address this, we expressed one linker under a muscle-specific promoter and the other under a ubiquitous promoter, delivered via AAV9 or AAV8. This approach achieved near-complete phenotypic restoration when administered neonatally and still provided significant benefit when given at progressed disease stages. Our strategy offers a mutation-independent, size-compatible, and potentially immune-tolerable treatment for LAMA2 MD with broad clinical potential. |
| HostingRepository | MassIVE |
| AnnounceDate | 2026-02-03 |
| AnnouncementXML | Submission_2026-02-03_06:42:28.173.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Thomas Bock |
| SpeciesList | scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Orbitrap Eclipse |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-07-24 04:44:57 | ID requested | |
| ⏵ 1 | 2026-02-03 06:42:28 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: LAMA2, Muscular Dystrophy, DatasetType:Proteomics |
Contact List
| Alexander Schmidt | |
|---|---|
| contact affiliation | Biozentrum, Universtiy of Basel, 4056 Basel, Switzerland |
| contact email | alex.schmidt@unibas.ch |
| lab head | |
| Thomas Bock | |
| contact affiliation | Uni Basel |
| contact email | thomas.bock@unibas.ch |
| 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-ftp.ucsd.edu/v10/MSV000098631/ |
