《自然—医学》杂志报道了一种恢复纤毛发育和嗅觉反应的基因疗法。这从原理上论证了基因疗法或可在特定遗传病中使用以恢复纤毛发育和修复感知功能。
纤毛是一种长在细胞表面的细胞器，纤毛病变是一组由纤毛结构和功能上的缺陷所导致的遗传病症。包括失明、听觉和嗅觉丧失在内的多种感知缺陷就可能伴随有这样的病变。
Jeffrey R. Martens等人发现细胞纤毛内转运蛋白88（IFT88）内的一种突变——IFT88是一种与人体纤毛病变有关的蛋白。该蛋白在实验小鼠体内的突变可导致鼻内神经细胞纤毛变短和畸变，从而使小鼠嗅觉失灵。研究人员发现，向病变小鼠鼻内神经细胞投送可表达IFT88的腺病毒载体能够修复纤毛的各种缺陷及神经细胞针对气味分子的反应。此外，他们还注意到基因疗法可以修复由实验小鼠嗅觉功能所调节的哺乳和摄食行为。（生物谷Bioon.com）
doi: 10.1038/nm.2860
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Gene therapy rescues cilia defects and restores olfactory function in a mammalian ciliopathy model
McIntyre JC, Davis EE, Joiner A, Williams CL, Tsai IC, Jenkins PM, McEwen DP, Zhang L, Escobado J, Thomas S, Szymanska K, Johnson CA, Beales PL, Green ED, Mullikin JC, Program NC, Sabo A, Muzny DM, Gibbs RA, Attié-Bitach T, Yoder BK, Reed RR, Katsanis N, Martens JR.
Cilia are evolutionarily conserved microtubule-based organelles that are crucial for diverse biological functions, including motility, cell signaling and sensory perception. In humans, alterations in the formation and function of cilia manifest clinically as ciliopathies, a growing class of pleiotropic genetic disorders. Despite the substantial progress that has been made in identifying genes that cause ciliopathies, therapies for these disorders are not yet available to patients. Although mice with a hypomorphic mutation in the intraflagellar transport protein IFT88 (Ift88(Tg737Rpw) mice, also known as ORPK mice) have been well studied, the relevance of IFT88 mutations to human pathology is unknown. We show that a mutation in IFT88 causes a hitherto unknown human ciliopathy. In vivo complementation assays in zebrafish and mIMCD3 cells show the pathogenicity of this newly discovered allele. We further show that ORPK mice are functionally anosmic as a result of the loss of cilia on their olfactory sensory neurons (OSNs). Notably, adenoviral-mediated expression of IFT88 in mature, fully differentiated OSNs of ORPK mice is sufficient to restore ciliary structures and rescue olfactory function. These studies are the first to use in vivo therapeutic treatment to reestablish cilia in a mammalian ciliopathy. More broadly, our studies indicate that gene therapy is a viable option for cellular and functional rescue of the complex ciliary organelle in established differentiated cells
