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Htra2

Prevention of acquired sensorineural hearing loss by in vivo Htra2 gene editing

March 22, 2021

CATEGORY:
Research

SCREENSHOT:
Prevention of acquired sensorineural hearing loss in mice by in vivo Htra2 gene editing

TITLE:
Prevention of acquired sensorineural hearing loss in mice by in vivo Htra2 gene editing

CONTENT:
Genome Biol. 2021 Mar 22;22(1):86. doi: 10.1186/s13059-021-02311-4.

ABSTRACT

BACKGROUND: Aging, noise, infection, and ototoxic drugs are the major causes of human acquired sensorineural hearing loss, but treatment options are limited. CRISPR/Cas9 technology has tremendous potential to become a new therapeutic modality for acquired non-inherited sensorineural hearing loss. Here, we develop CRISPR/Cas9 strategies to prevent aminoglycoside-induced deafness, a common type of acquired non-inherited sensorineural hearing loss, via disrupting the Htra2 gene in the inner ear which is involved in apoptosis but has not been investigated in cochlear hair cell protection.

RESULTS: The results indicate that adeno-associated virus (AAV)-mediated delivery of CRISPR/SpCas9 system ameliorates neomycin-induced apoptosis, promotes hair cell survival, and significantly improves hearing function in neomycin-treated mice. The protective effect of the AAV-CRISPR/Cas9 system in vivo is sustained up to 8 weeks after neomycin exposure. For more efficient delivery of the whole CRISPR/Cas9 system, we also explore the AAV-CRISPR/SaCas9 system to prevent neomycin-induced deafness. The in vivo editing efficiency of the SaCas9 system is 1.73% on average. We observed significant improvement in auditory brainstem response thresholds in the injected ears compared with the non-injected ears. At 4 weeks after neomycin exposure, the protective effect of the AAV-CRISPR/SaCas9 system is still obvious, with the improvement in auditory brainstem response threshold up to 50 dB at 8 kHz.

CONCLUSIONS: These findings demonstrate the safe and effective prevention of aminoglycoside-induced deafness via Htra2 gene editing and support further development of the CRISPR/Cas9 technology in the treatment of non-inherited hearing loss as well as other non-inherited diseases.

PMID:33752742 | DOI:10.1186/s13059-021-02311-4

SOURCE:
Genome biology

PUBLISHER:

PMID:
pubmed:33752742

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33752742

DOI:
10.1186/s13059-021-02311-4

DATE – PUBLISHED:
Tue, 23 Mar 2021 06:00:00 -0400

DATE – DOI:
2021-03-22T09:13:12Z

DATE – ADDED:
03/23/21 07:24AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33752742/

LINK – DOI:
https://doi.org/10.1186/s13059-021-02311-4

LINK – PUBLISHER:
https://genomebiology.biomedcentral.com/articles/10.1186/s13059-021-02311-4?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-23T11:24:13+00:00, https://www.hearinglosstreatmentreport.com.

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