PXD032891

PXD032891 is an original dataset announced via ProteomeXchange.

Title	Direct Evolution of Adeno-Associated Virus 5 Capsid Enables Specific Liver Tropism
Description	Gene therapy has been thriving in recent years, as featured by general triumphs in several clinical trials to treat hemophilia. It highlights the significance of AAV mediated gene delivery to liver. AAV5 is a unique serotype with low neutralizing antibody prevalence. In this study, we generated an AAV5 mutant vector by inserting an oligopeptide into the variable region VIII of the AAV5, termed as AAVzk2, which displayed comparable yield with wild type serotypes. Mice intravenously injected with AAVzk2 demonstrated a stronger liver transduction than AAV5, which were grossly comparable with AAV8 and 9 treated mice. However, AAVzk2 negligibly transduced other tissues or organs such as heart, lung, spleen, kidney, brain and skeletal muscle, indicating a liver specific tropism. Further studies showed a superior human hepatocellular transduction of AAVzk2 to AAV5, 8 and 9, whereas the seroreactivity of AAVzk2 was as low as AAV5. Moreover, mass spectroscopy revealed great divergency in post-translational modification patterns between AAV5 and AAVzk2. Overall, we provide a novel AAV serotype that could not only facilitate a robust and specific liver gene delivery to a large population, but also offer valuable clues for future investigation of the nature of AAV5.
HostingRepository	iProX
AnnounceDate	2022-04-01
AnnouncementXML	Submission_2023-08-14_00:31:39.619.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yuqiu Wang
SpeciesList	scientific name: Adeno-associated virus - 5; NCBI TaxID: 82300;
ModificationList	deaminated residue; phosphorylated residue; ubiquitination signature dipeptidyl lysine; monomethylated residue; O-glycosyl-L-serine; O-glycosyl-L-threonine
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-01 05:57:59	ID requested
1	2022-04-01 05:58:16	announced
⏵ 2	2023-08-14 00:31:40	announced	2023-08-14: Update publication information.

Wang Y, Yang C, Hu H, Chen C, Yan M, Ling F, Wang KC, Wang X, Deng Z, Zhou X, Zhang F, Lin S, Du Z, Zhao K, Xiao X, Directed evolution of adeno-associated virus 5 capsid enables specific liver tropism. Mol Ther Nucleic Acids, 28():293-306(2022) [pubmed]

submitter keyword: AAV5, novel capsid, liver tropism, low seroreactivity

Hu zhou
contact affiliation	Shanghai Institute of Materia Medica
contact email	zhouhu@simm.ac.cn
lab head
Yuqiu Wang
contact affiliation	East China University of Science and Technology
contact email	995752924@qq.com
dataset submitter

iProX dataset URI