更新于：2024-11-01

FAM161A

更新于：2024-11-01

基本信息

别名

FAM161 centrosomal protein A、FAM161A、FLJ13305

+ [2]

简介

Involved in ciliogenesis.

关联

项与 FAM161A 相关的药物

WO2024013224

专利挖掘

靶点

FAM161A

作用机制-

在研机构

Hadasit Medical Research Services & Development Ltd.

原研机构

Fondation Asile des aveugles [+1]

在研适应症

眼部疾病

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 FAM161A 相关的临床结果

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100 项与 FAM161A 相关的转化医学

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0 项与 FAM161A 相关的专利（医药）

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项与 FAM161A 相关的文献（医药）

2024-10-15·Cells

A Comparative Analysis of Models for AAV-Mediated Gene Therapy for Inherited Retinal Diseases.

Review

作者: Kuznetsova, Ekaterina ; Nadzhafova, Aygun ; Antonova, Ekaterina ; Pavlov, Roman ; Mityaeva, Olga ; Kadyshev, Vitaly ; Gornostal, Ekaterina ; Kolotova, Daria ; Mingaleva, Natalia ; Alsalloum, Almaqdad ; Volchkov, Pavel

Inherited retinal diseases (IRDs) represent a diverse group of genetic disorders leading to progressive degeneration of the retina due to mutations in over 280 genes. This review focuses on the various methodologies for the preclinical characterization and evaluation of adeno-associated virus (AAV)-mediated gene therapy as a potential treatment option for IRDs, particularly focusing on gene therapies targeting mutations, such as those in the RPE65 and FAM161A genes. AAV vectors, such as AAV2 and AAV5, have been utilized to deliver therapeutic genes, showing promise in preserving vision and enhancing photoreceptor function in animal models. Despite their advantages-including high production efficiency, low pathogenicity, and minimal immunogenicity-AAV-mediated therapies face limitations such as immune responses beyond the retina, vector size constraints, and challenges in large-scale manufacturing. This review systematically compares different experimental models used to investigate AAV-mediated therapies, such as mouse models, human retinal explants (HREs), and induced pluripotent stem cell (iPSC)-derived retinal organoids. Mouse models are advantageous for genetic manipulation and detailed investigations of disease mechanisms; however, anatomical differences between mice and humans may limit the translational applicability of results. HREs offer valuable insights into human retinal pathophysiology but face challenges such as tissue degradation and lack of systemic physiological effects. Retinal organoids, on the other hand, provide a robust platform that closely mimics human retinal development, thereby enabling more comprehensive studies on disease mechanisms and therapeutic strategies, including AAV-based interventions. Specific outcomes targeted in these studies include vision preservation and functional improvements of retinas damaged by genetic mutations. This review highlights the strengths and weaknesses of each experimental model and advocates for their combined use in developing targeted gene therapies for IRDs. As research advances, optimizing AAV vector design and delivery methods will be critical for enhancing therapeutic efficacy and improving clinical outcomes for patients with IRDs.

2024-09-01·Open Biology

Fly Fam161 is an essential centriole and cilium transition zone protein with unique and diverse cell type-specific localizations

Article

作者: Jaiswal, Ankit ; Boring, Andrew ; Avidor-Reiss, Tomer ; Mukherjee, Avik

Family with sequence similarity 161 (Fam161) is an ancient family of microtubule-binding proteins located at the centriole and cilium transition zone (TZ) lumen that exhibit rapid evolution in mice. However, their adaptive role is unclear. Here, we used flies to gain insight into their cell type-specific adaptations. Fam161 is the sole orthologue of FAM161A and FAM161B found in flies. Mutating Fam161 results in reduced male reproduction and abnormal geotaxis behaviour. Fam161 localizes to sensory neuron centrioles and their specialized TZ (the connecting cilium) in a cell type-specific manner, sometimes labelling only the centrioles, sometimes labelling the centrioles and cilium TZ and sometimes labelling the TZ with varying lengths that are longer than other TZ proteins, defining a new ciliary compartment, the extra distal TZ. These findings suggest that Fam161 is an essential centriole and TZ protein with a unique cell type-specific localization in fruit flies that can produce cell type-specific adaptations.

2024-08-05·Journal of Cell Biology

Poc1 bridges basal body inner junctions to promote triplet microtubule integrity and connections

Article

作者: Li, Sam ; Ruehle, Marisa D ; Agard, David A ; Pearson, Chad G

Basal bodies (BBs) are conserved eukaryotic structures that organize cilia. They are comprised of nine, cylindrically arranged, triplet microtubules (TMTs) connected to each other by inter-TMT linkages which stabilize the structure. Poc1 is a conserved protein important for BB structural integrity in the face of ciliary forces transmitted to BBs. To understand how Poc1 confers BB stability, we identified the precise position of Poc1 in the Tetrahymena BB and the effect of Poc1 loss on BB structure. Poc1 binds at the TMT inner junctions, stabilizing TMTs directly. From this location, Poc1 also stabilizes inter-TMT linkages throughout the BB, including the cartwheel pinhead and the inner scaffold. The full localization of the inner scaffold protein Fam161A requires Poc1. As ciliary forces are increased, Fam161A is reduced, indicative of a force-dependent molecular remodeling of the inner scaffold. Thus, while not essential for BB assembly, Poc1 promotes BB interconnections that establish an architecture competent to resist ciliary forces.