PXD047487

PXD047487 is an original dataset announced via ProteomeXchange.

Title	A novel capsid-XL32-derived adeno-associated virus serotype prompts retinal tropism and ameliorates choroidal neovascularization
Description	Gene therapy has been adapted, from the laboratory to the clinic, to treat retinopathies. In contrast to subretinal route, intravitreal delivery of AAV vectors displays the advantage of bypassing surgical injuries, but the viral particles are more prone to be nullified by the host neutralizing factors. To minimize such suppression of therapeutic effect, especially in terms of AAV2 and its derivatives, we introduced three serine-to-glycine mutations, based on the phosphorylation sites identified by mass spectrum analysis, to the XL32 capsid to generate a novel serotype named AAVYC5. Via intravitreal administration, AAVYC5 was transduced more effectively into multiple retinal layers compared with AAV2 and XL32. AAVYC5 also enabled successful delivery of anti-angiogenic molecules to rescue laser-induced choroidal neovascularization and astrogliosis in mice and non-human primates. Furthermore, we detected fewer neutralizing antibodies and binding IgG in human sera against AAVYC5 than those specific for AAV2 and XL32. Our results thus implicate this capsid-optimized AAVYC5 as a promising vector suitable for a wide population, particularly those with undesirable AAV2 seroreactivity.
HostingRepository	iProX
AnnounceDate	2023-12-04
AnnouncementXML	Submission_2024-05-15_01:17:25.908.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yuqiu Wang
SpeciesList	scientific name: Adeno-Associated Virus PREDICT_AaV-6; NCBI TaxID: 1717199;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-03 19:47:57	ID requested
1	2023-12-03 19:54:48	announced
⏵ 2	2024-05-15 01:17:26	announced	2024-05-15: Update information.

Luo LL, Xu J, Wang BQ, Chen C, Chen X, Hu QM, Wang YQ, Zhang WY, Jiang WX, Li XT, Zhou H, Xiao X, Zhao K, Lin S, A novel capsid-XL32-derived adeno-associated virus serotype prompts retinal tropism and ameliorates choroidal neovascularization. Biomaterials, 304():122403(2024) [pubmed]

submitter keyword: AAVXL32

Hu Zhou
contact affiliation	Shanghai Institute of Materia Medica
contact email	zhouhu@simm.ac.cn
lab head
Yuqiu Wang
contact affiliation	Shanghai Institute of Materia Medica
contact email	995752924@qq.com
dataset submitter

iProX dataset URI