确定SLC35A1作为转导多血清组合复合腺相关病毒 (AAV) 载体的重要宿主因子
Xiujuan Zhang1, Siyuan Hao1, Zehua Feng2
1Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
bioRxiv : the preprint server for biology
|October 28, 2024
概括
溶解物载体家族35个成员A1 (SLC35A1) 载体对腺相关病毒 (AAV) 载体转导至关重要. SLC35A1的淘汰会损害AAV的核导入,并影响跨多个血清型的转导.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 细胞生物学 细胞生物学
背景情况:
- 基因相关病毒 (AAV) 载体是基因治疗的有希望的工具.
- 了解影响AAV转导的宿主因素对于优化基因传递至关重要.
- 之前的查发现KIAA039L,TM9SF2和RNF121是rAAV5.5的宿主因素.
研究的目的:
- 研究溶解物载体家族35个成员A1 (SLC35A1) 在AAV转导中的作用.
- 阐明SLC35A1影响AAV细胞内贩运和核进口的机制.
主要方法:
- 在293-F细胞中进行全基因组的CRISPR/Cas9选.
- 产生和分析SLC35A1淘汰赛 (KO) 和突变细胞系.
- 量化AAV转导效率,细胞表面酸表达和载体核进口.
主要成果:
- SLC35A1 KO显著降低了rAAV5转导和改变了细胞表面酸表达.
- SLC35A1 KO影响了多个AAV血清型的转导,增加了一些 (例如,rAAV9,rAAV11) 和减少其他 (例如,rAAV2,rAAV3).
- SLC35A1 KO显著影响了AAV载体的核导入,C端尾对这一过程至关重要.
结论:
- 在一些血清型中,SLC35A1在AAV载体转导中发挥着重要作用,独立于某些血清型的直接酸结合.
- 丁5'-单酸-酸 (CMP-SIA) 载体参与了AAV载体的内部化后细胞内贩运.
- SLC35A1的C端细胞质尾部对于有效的AAV转导和核导入至关重要.
相关概念视频
01:03Rous Sarcoma Virus (RSV) and Cancer
Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
01:23Cystic Fibrosis: Pathogenesis
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...
01:29Respiratory Syncytial Virus Disease
Human respiratory syncytial virus (RSV) is a widespread pathogen that primarily targets infants and young children but also poses a serious health risk to elderly and immunocompromised individuals. Belonging to the Pneumoviridae family, RSV is a negative-sense, single-stranded RNA virus within the Pneumovirus genus. Its global health burden is significant, with millions of cases annually resulting in hospitalizations and mortality, particularly in resource-limited settings. Although most...