Evidence map›Paper›PMID 33752742›Full record

ArticleGenome biology2021

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

Xi Gu, Daqi Wang, Zhijiao Xu, Jinghan Wang, Luo Guo, Renjie Chai, Genglin Li, Yilai Shu, Huawei Li

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.7field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 52 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Advancing precision ear medicine: leveraging animal models for disease insights and therapeutic innovations.Mammalian genome : official journal of the International Mammalian Genome Society · 2025
    Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Extracellular vesicles for developing targeted hearing loss therapy.Journal of controlled release : official journal of the Controlled Release Society · 2024
    Review
  11. Review
  12. Article
  13. [Study on gene therapy for DPOAE and ABR threshold changes in adultLin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2024
    Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. Rescue of hearing by adenine base editing in a humanized mouse model of Usher syndrome type 1F.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Xi Gu *ENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200031, China.
Daqi Wang *ENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200031, China.
Zhijiao Xu *ENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200031, China.
Jinghan WangENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200031, China.
Luo GuoENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200031, China.
Renjie ChaiKey Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, 210096, China.
Genglin LiENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200031, China.
Yilai Shu *ENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200031, China. yilai_shu@fudan.edu.cn.ORCID 0000-0001-8893-434X
Huawei Li *ENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200031, China. hwli@shmu.edu.cn.
Fudan University · CNFujian Medical University · CNNantong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAging, 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.

resultsThe 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.

conclusionsThese 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.

Indexed as

CRISPR-Cas SystemsGene EditingAnimalsCell LineCell SurvivalDependovirusDisease Models, AnimalGene ExpressionGene TargetingGenetic EngineeringGenetic TherapyGenetic VectorsHair Cells, AuditoryHearing Loss, SensorineuralHearing TestsHigh-Temperature Requirement A Serine Peptidase 2High-Temperature Requirement A Serine Peptidase 2Htra2 protein, mouseRNA, Guide, CRISPR-Cas SystemsAminoglycoside antibioticsAnti-apoptosisCochleaCRISPR/Cas9Genome editingHair cellOmi/HtrA2Ototoxic deafness

Identifiers

PMID33752742
PMCPMC7983387
OpenAlexW3138115672

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.