Nat Commun:治疗失明新策略!利用CRISPR阻止视网膜退化!

2017-03-16 生物谷 生物谷

根据一项新的研究,在小鼠体内,沉默基因Nrl会阻止视网膜退行性疾病中的细胞丢失。这一发现可能导致人们开发出新的疗法来阻止视网膜色素变性等人类疾病中的视力丧失。这项研究是由来自美国国家眼科研究所(NEI)的研究人员开展的。相关研究结果于2017年3月14日在线发表在Nature C


图片来自图片来自Zhijian Wu和Anand Swaroop。

根据一项新的研究,在小鼠体内,沉默基因Nrl会阻止视网膜退行性疾病中的细胞丢失。这一发现可能导致人们开发出新的疗法来阻止视网膜色素变性等人类疾病中的视力丧失。这项研究是由来自美国国家眼科研究所(NEI)的研究人员开展的。相关研究结果于2017年3月14日在线发表在Nature Communications期刊上,论文标题为“Nrl knockdown by AAV-delivered CRISPR/Cas9 prevents retinal degeneration in mice”。NEI是美国国家卫生研究院(NIH)的一部分。

在眼球后的视网膜组织含有两种类型的感光细胞:视杆细胞(能感受弱光)和视锥细胞(主司昼视觉,有色视觉)。它们能够将光转化为发送到大脑中的电信号。基因突变主要影响视杆细胞,导致夜盲症,如视网膜色素变性中观察到的视力丧失。然而,鉴于视杆细胞也给视锥细胞提供至关重要的结构和营养支持,视杆细胞功能障碍或死亡能够导致视锥细胞退化和失明。

在一系列研究中,NEI神经退化与修复实验室主任Anand Swaroop博士和他的团队想要知道拯救视杆细胞是否能够阻止视锥细胞丢失,从而保留昼视觉(daylight vision)和色视觉(color vision)。

在发育期间,Nrl决定着视杆细胞前体细胞是变成视杆细胞或还是变成视锥细胞。在之前的研究中,Swaroop和同事们证实经基因改造缺乏Nrl基因的小鼠产生仅含有视锥细胞的视网膜。其他的科学家们证实如果在成年小鼠的视杆细胞中敲除Nrl基因,那么这些视杆细胞虽然存在基因突变,但是会获得类似于视锥细胞的特征。

Swaroop说,“对我们而言,这一证据提示着通过敲除Nrl基因诱导视杆细胞变得更加类似于视锥细胞是一种压制导致视杆细胞退化的基因突变的潜在策略。因此,附近的视锥细胞将保持功能性和活力。”

为了测试这种策略,这些研究人员采用了一种新的被称作CRISPR的基因组编辑技术。CRISPR类似于一对分子剪刀,能够经编程后精准地切割特定的DNA序列。

论文第一作者、NEI博士后研究员Wenhan Yu博士开发出一种将CRISPR用于视网膜感光细胞中的方法。他的策略利用腺相关病毒(AAV)作为载体,将CRISPR导入视网膜感光细胞中。Yu测试了这种基因组编辑工具:移除野生小鼠和三种不同的视网膜退化模式小鼠体内的Nrl基因。通过测量基因表达和研究这些视网膜感光细胞,这些研究人员证实正如预测中的一样,视杆细胞变得更加类似于视锥细胞。尽管这些类似于视锥细胞的视杆细胞不能够检测光线,但是它们存活下来,改善它们附近的视锥细胞存活。

在这三种模式小鼠体内,这种疗法会阻止或延缓视杆细胞退化,不过它实现的益处不如当在年老的小鼠体内开展这种疗法时所实现的那么大。重要的是,不论小鼠发生何种特定的基因缺陷,这种疗法在这三种模式小鼠体内的益处是显而易见的。

论文通信作者、NEI眼科基因疗法中心主任Zhijian Wu博士解释道,“不同于常见的基因疗法:导入正常的基因替换存在缺陷的基因,这种方法可能能够治疗由多种突变基因导致的视网膜退化。”

在能够在临床试验中测试这种疗法之前,还需要开展更多的研究。迄今为止,还未确定CRISPR的安全性,而且还需了解关于它可能存在的副作用的信息。然而,这些发现为开发基于CRISPR治疗视网膜退行性疾病的疗法提供概念验证。

原始出处:

Wenhan Yu, Suddhasil Mookherjee, Vijender Chaitankar et al. Nrl knockdown by AAV-delivered CRISPR/Cas9 prevents retinal degeneration in mice. Nature Communications, Published online:14 March 2017, doi:10.1038/ncomms14716


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    2017-07-03 liye789132251
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    2017-12-15 liuli5079
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channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20161026/IMG58107C0F82E499574.jpg, createdBy=00e81970035, createdName=1e15b6fem30(暂无匿称), createdTime=Thu Mar 16 19:30:22 CST 2017, time=2017-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180389, encodeId=f1d1180389f8, content=学习了,非常好的研究,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6b0d1671629, createdName=1de11f7fm56(暂无匿称), createdTime=Thu Mar 16 19:15:19 CST 2017, time=2017-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180381, encodeId=e0141803814a, content=谢谢分享,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Thu Mar 16 18:31:06 CST 2017, time=2017-03-16, status=1, ipAttribution=)]
    2017-03-17 zutt
  4. 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attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo5nmIH5IQqCKjJgSCuicPWUWOUcdqt1ROPnEiaOYN4pSHibDv8la3OxNLalvuvUXn8clpJlrpuyTpckgt9OPkeSSdT/0, createdBy=8fd71930726, createdName=半夏微凉, createdTime=Fri Mar 17 06:02:19 CST 2017, time=2017-03-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180423, encodeId=34ec18042368, content=好好学习,涨知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zSn0GqHrsfLANEL7Sww3HicKsN9aribicAmGGWXOIMEiaZ1iadgZg9RibjqSwIKUS8gSPib2NwTVg2zVvVJhdP3BkuDIl/0, createdBy=944d1605392, createdName=shaosai, createdTime=Thu Mar 16 22:22:58 CST 2017, time=2017-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180394, encodeId=59bc180394b6, content=很好的学习资料,谢谢了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20161026/IMG58107C0F82E499574.jpg, createdBy=00e81970035, createdName=1e15b6fem30(暂无匿称), createdTime=Thu Mar 16 19:30:22 CST 2017, time=2017-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180389, encodeId=f1d1180389f8, content=学习了,非常好的研究,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6b0d1671629, createdName=1de11f7fm56(暂无匿称), createdTime=Thu Mar 16 19:15:19 CST 2017, time=2017-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180381, encodeId=e0141803814a, content=谢谢分享,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Thu Mar 16 18:31:06 CST 2017, time=2017-03-16, status=1, ipAttribution=)]
    2017-03-17 yuandd
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  6. 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channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20161026/IMG58107C0F82E499574.jpg, createdBy=00e81970035, createdName=1e15b6fem30(暂无匿称), createdTime=Thu Mar 16 19:30:22 CST 2017, time=2017-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180389, encodeId=f1d1180389f8, content=学习了,非常好的研究,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6b0d1671629, createdName=1de11f7fm56(暂无匿称), createdTime=Thu Mar 16 19:15:19 CST 2017, time=2017-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180381, encodeId=e0141803814a, content=谢谢分享,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Thu Mar 16 18:31:06 CST 2017, time=2017-03-16, status=1, ipAttribution=)]
    2017-03-17 半夏微凉

    学习了谢谢分享

    0

  7. 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topicName=CRISPR)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=583c133, createdName=yuandd, createdTime=Fri Mar 17 21:34:00 CST 2017, time=2017-03-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1478386, encodeId=23fc14e8386b9, content=<a href='/topic/show?id=d1a55858e70' target=_blank style='color:#2F92EE;'>#新策略#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58587, encryptionId=d1a55858e70, topicName=新策略)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=da0f7431516, createdName=12498568m52暂无昵称, createdTime=Fri Mar 17 21:34:00 CST 2017, time=2017-03-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180489, encodeId=2a4c180489ba, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo5nmIH5IQqCKjJgSCuicPWUWOUcdqt1ROPnEiaOYN4pSHibDv8la3OxNLalvuvUXn8clpJlrpuyTpckgt9OPkeSSdT/0, createdBy=8fd71930726, createdName=半夏微凉, createdTime=Fri Mar 17 06:02:19 CST 2017, time=2017-03-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180423, encodeId=34ec18042368, content=好好学习,涨知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zSn0GqHrsfLANEL7Sww3HicKsN9aribicAmGGWXOIMEiaZ1iadgZg9RibjqSwIKUS8gSPib2NwTVg2zVvVJhdP3BkuDIl/0, createdBy=944d1605392, createdName=shaosai, createdTime=Thu Mar 16 22:22:58 CST 2017, time=2017-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180394, encodeId=59bc180394b6, content=很好的学习资料,谢谢了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20161026/IMG58107C0F82E499574.jpg, createdBy=00e81970035, createdName=1e15b6fem30(暂无匿称), createdTime=Thu Mar 16 19:30:22 CST 2017, time=2017-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180389, encodeId=f1d1180389f8, content=学习了,非常好的研究,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6b0d1671629, createdName=1de11f7fm56(暂无匿称), createdTime=Thu Mar 16 19:15:19 CST 2017, time=2017-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180381, encodeId=e0141803814a, content=谢谢分享,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Thu Mar 16 18:31:06 CST 2017, time=2017-03-16, status=1, ipAttribution=)]
    2017-03-16 shaosai

    好好学习,涨知识

    0

  8. 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channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20161026/IMG58107C0F82E499574.jpg, createdBy=00e81970035, createdName=1e15b6fem30(暂无匿称), createdTime=Thu Mar 16 19:30:22 CST 2017, time=2017-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180389, encodeId=f1d1180389f8, content=学习了,非常好的研究,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6b0d1671629, createdName=1de11f7fm56(暂无匿称), createdTime=Thu Mar 16 19:15:19 CST 2017, time=2017-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180381, encodeId=e0141803814a, content=谢谢分享,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Thu Mar 16 18:31:06 CST 2017, time=2017-03-16, status=1, ipAttribution=)]
    2017-03-16 1e15b6fem30(暂无匿称)

    很好的学习资料,谢谢了。

    0

  9. 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channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20161026/IMG58107C0F82E499574.jpg, createdBy=00e81970035, createdName=1e15b6fem30(暂无匿称), createdTime=Thu Mar 16 19:30:22 CST 2017, time=2017-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180389, encodeId=f1d1180389f8, content=学习了,非常好的研究,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6b0d1671629, createdName=1de11f7fm56(暂无匿称), createdTime=Thu Mar 16 19:15:19 CST 2017, time=2017-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180381, encodeId=e0141803814a, content=谢谢分享,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Thu Mar 16 18:31:06 CST 2017, time=2017-03-16, status=1, ipAttribution=)]
    2017-03-16 1de11f7fm56(暂无匿称)

    学习了,非常好的研究,谢谢分享

    0

  10. 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channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20161026/IMG58107C0F82E499574.jpg, createdBy=00e81970035, createdName=1e15b6fem30(暂无匿称), createdTime=Thu Mar 16 19:30:22 CST 2017, time=2017-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180389, encodeId=f1d1180389f8, content=学习了,非常好的研究,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6b0d1671629, createdName=1de11f7fm56(暂无匿称), createdTime=Thu Mar 16 19:15:19 CST 2017, time=2017-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180381, encodeId=e0141803814a, content=谢谢分享,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Thu Mar 16 18:31:06 CST 2017, time=2017-03-16, status=1, ipAttribution=)]
    2017-03-16 明月清辉

    谢谢分享,学习了

    0

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