| 项目编号 |
PRJCA010559 |
| 项目标题 |
AAV-mediated gene therapy produces fertile offspring in the Lhcgr-deficient mouse model of Leydig cell failure |
| 涉及领域 |
Medical |
| 数据类型 |
Transcriptome or Gene expression
|
| 物种名称 |
Mus musculus
|
| 描述信息 |
Leydig cell failure (LCF) caused by gene mutation results in testosterone deficiency and infertility. Serum testosterone levels can be recovered via testosterone replacement; however, established therapies have shown limited success in restoring fertility. Here, we used a luteinizing hormone/choriogonadotrophin receptor (Lhcgr)-deficient mouse model of genetic LCF to investigate the feasibility of gene therapy for restoring testosterone production and fertility. We screened several adeno-associated virus (AAV) serotypes and identified AAV8 as an efficient vector to drive exogenous Lhcgr expression in progenitor Leydig cells through interstitial injection. We observed considerable testosterone recovery and Leydig cell maturation after AAV8-Lhcgr treatment in pubertal Lhcgr-/- mice. This gene therapy substantially recovered sexual development, partially restored spermatogenesis and effectively produced fertile offspring. Furthermore, these favorable effects could be reproduced in adult Lhcgr-/- mice. Our proof-of-concept experiments in this mouse model demonstrate that AAV-mediated gene therapy may represent a promising therapeutic approach for patients with genetic LCF. |
| 样品范围 |
Multiisolate |
| 发布日期 |
2022-11-28 |
| 出版信息 |
| PubMed ID |
文章标题 |
杂志名称 |
Doi |
发表年份 |
| 36270285
|
AAV-mediated gene therapy produces fertile offspring in the Lhcgr-deficient mouse model of Leydig cell failure
|
Cell Reports Medicine
|
10.1016/j.xcrm.2022.100792
|
2022
|
|
|
| 项目资金来源 |
| 机构 |
项目类型 |
授权项目ID |
授权项目名称 |
| National Key Research and Development Program of China
|
|
2017YFA0103802
|
|
|
|
| 提交者 |
Chunhua
Deng (dengchh@mail.sysu.edu.cn)
|
| 提交单位 |
The First Affiliated Hospital, Sun Yat-sen University |
| 提交日期 |
2022-07-17 |
