Optimized AAV capsids for basal ganglia diseases show robust potency and distribution

D. E. Leib, Y. H. Chen, L. Tecedor, P. T. Ranum, M. S. Keiser, B. C. Lewandowski, E. M. Carrell, S. Arora, I. Huerta-Ocampo, D. Lai, C. M. Fluta, C. Cheng, X. Liu and B. L. Davidson ()
Additional contact information
D. E. Leib: The Children’s Hospital of Philadelphia
Y. H. Chen: The Children’s Hospital of Philadelphia
L. Tecedor: The Children’s Hospital of Philadelphia
P. T. Ranum: The Children’s Hospital of Philadelphia
M. S. Keiser: The Ohio State University
B. C. Lewandowski: The Children’s Hospital of Philadelphia
E. M. Carrell: The Children’s Hospital of Philadelphia
S. Arora: The Children’s Hospital of Philadelphia
I. Huerta-Ocampo: The Children’s Hospital of Philadelphia
D. Lai: The Children’s Hospital of Philadelphia
C. M. Fluta: Latus Bio
C. Cheng: The Children’s Hospital of Philadelphia
X. Liu: The Children’s Hospital of Philadelphia
B. L. Davidson: The Children’s Hospital of Philadelphia

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Huntington’s disease and other disorders of the basal ganglia create challenges for biomolecule-based medicines given the poor accessibility of these deep brain structures following intracerebral or intravascular delivery. Here, we found that low dose, low volume delivery of unbiased AAV libraries into the globus pallidus allowed recovery of novel capsids capable of broad access to key deep brain and cortical structures relevant for human therapies. One such capsid, AAV-DB-3, provided transduction of up to 45% of medium spiny neurons in the adult NHP striatum, along with substantial transduction of relevant deep layer neurons in the cortex. Notably, AAV-DB-3 behaved similarly in mice as in NHPs and potently transduced human neurons derived from induced pluripotent stem cells. Thus, AAV-DB-3 provides a unique AAV for network level brain gene therapies that translates up and down the evolutionary scale for preclinical studies and eventual clinical use.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-60000-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60000-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-60000-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().