Cochlear transduction via cerebrospinal fluid delivery of AAV in non-human primates.

Mol Ther

Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Published: March 2023


Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10014218PMC
http://dx.doi.org/10.1016/j.ymthe.2022.12.018DOI Listing

Publication Analysis

Top Keywords

cochlear transduction
4
transduction cerebrospinal
4
cerebrospinal fluid
4
fluid delivery
4
delivery aav
4
aav non-human
4
non-human primates
4
cochlear
1
cerebrospinal
1
fluid
1

Similar Publications

Magnetic Targeting of AAV Gene Therapy for Inner Ear Following Systemic Delivery: Preliminary Findings and Transduction Pattern in Rat Cochlea.

J Assoc Res Otolaryngol

September 2025

Biological Sciences Platform, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room M1 102, Toronto, ON, M4N 3M5, Canada.

Purpose: Delivery of therapeutics to the inner ear is complicated by their inaccessible location and the presence of the blood-labyrinth barrier that restricts most blood-borne compounds from entering the inner ear. This study addresses the challenge of optimal delivery in treating inner ear disease, focusing on magnetic targeting gene therapy using adeno-associated virus (AAV).

Methods: The investigation explores three AAV serotypes (AAV2 Quad Mut, AAV2 pANC80L65, and AAV9 PHP.

View Article and Find Full Text PDF

The plasma membrane is actively regulated by lipid transporters that create electrochemical gradients between leaflets, and passively by scramblases that dissipate these gradients. Membrane properties such as lipid packing are critical for the proper function of transmembrane proteins, particularly mechanosensitive ion channels. Mechanosensation is a key component of many sensory processes including balance, and hearing.

View Article and Find Full Text PDF

Stereocilia are F-actin-based cylindrical protrusions on the apical surface of inner ear hair cells that function as biological mechanosensors of sound and acceleration. During stereocilia development, specific unconventional myosins transport proteins and phospholipids as cargo and mediate elongation, differentiation and acquisition of the mechanoelectrical transduction (MET). How unconventional myosins localize themselves and cargo in stereocilia using energy from ATP hydrolysis is only partially understood.

View Article and Find Full Text PDF

Hair cells within the inner ear cochlea are specialized mechanoreceptors required for hearing. Hair cells are not regenerated in mammals, and their loss is a leading cause of deafness in humans. Cochlear supporting cells in newborn mice have the capacity to regenerate hair cells, but persistent Notch signaling, presumably activated by the Notch ligand Jagged1, prevents supporting cells from converting into hair cells.

View Article and Find Full Text PDF

Background: Sodium salicylate (SS) causes hearing damage and tinnitus in humans and animals. Chlorogenic acid (CGA) has strong antioxidant and anti-apoptotic effects, but whether it can protect the cochlea is unknown.

Methods: SS was used to induce cochlear injury in rats, followed by 150, 300 and 600 mg/kg CGA treatment.

View Article and Find Full Text PDF