《自然—醫(yī)學(xué)》雜志報(bào)道了一種恢復(fù)纖毛發(fā)育和嗅覺反應(yīng)的基因療法,。這從原理上論證了基因療法或可在特定遺傳病中使用以恢復(fù)纖毛發(fā)育和修復(fù)感知功能,。
纖毛是一種長在細(xì)胞表面的細(xì)胞器,，纖毛病變是一組由纖毛結(jié)構(gòu)和功能上的缺陷所導(dǎo)致的遺傳病癥,。包括失明,、聽覺和嗅覺喪失在內(nèi)的多種感知缺陷就可能伴隨有這樣的病變,。
Jeffrey R. Martens等人發(fā)現(xiàn)細(xì)胞纖毛內(nèi)轉(zhuǎn)運(yùn)蛋白88（IFT88）內(nèi)的一種突變——IFT88是一種與人體纖毛病變有關(guān)的蛋白,。該蛋白在實(shí)驗(yàn)小鼠體內(nèi)的突變可導(dǎo)致鼻內(nèi)神經(jīng)細(xì)胞纖毛變短和畸變,，從而使小鼠嗅覺失靈,。研究人員發(fā)現(xiàn)，向病變小鼠鼻內(nèi)神經(jīng)細(xì)胞投送可表達(dá)IFT88的腺病毒載體能夠修復(fù)纖毛的各種缺陷及神經(jīng)細(xì)胞針對氣味分子的反應(yīng),。此外,，他們還注意到基因療法可以修復(fù)由實(shí)驗(yàn)小鼠嗅覺功能所調(diào)節(jié)的哺乳和攝食行為。（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
