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Biomaterials:通过Cas9/sgRNA编辑制备DNA适体免疫检查点

2019-07-28 不详 网络

免疫检查点抑制剂已在免疫疗法中广泛研究。尽管抗体已被更广泛地用于阻断免疫检查点,但DNA适体具有用于此目的的独特优势。在这里,我们设计了一种DNA多聚体水凝胶,可以通过Cas9/sgRNA精确切割,用于编程释放免疫检查点-阻断DNA适体。作为代表性免疫检查点抑制剂,我们使用PD-1 DNA适体。使用滚环扩增产生包含具有PD-1适体和sgRNA靶向序列的DNA的水凝胶。当与Cas9/sgRNA混合时

免疫检查点抑制剂已在免疫疗法中广泛研究。尽管抗体已被更广泛地用于阻断免疫检查点,但DNA适体具有用于此目的的独特优势。在这里,我们设计了一种DNA多聚体水凝胶,可以通过Cas9/sgRNA精确切割,用于编程释放免疫检查点-阻断DNA适体。

作为代表性免疫检查点抑制剂,我们使用PD-1 DNA适体。使用滚环扩增产生包含具有PD-1适体和sgRNA靶向序列的DNA的水凝胶。当与Cas9/sgRNA混合时,PD-1 DNA适体水凝胶(PAH)失去其凝胶特性并释放PD-1适体序列。凝胶电泳证实,精确的Cas9/sgRNA介导的PD-1 DNA适体的释放可有效激活脾细胞的细胞因子分泌功能。在体内,分子成像显示,与Cas9/sgRNA(Cas9/PAH)共注射的PD-1 DNA多聚体水凝胶在游离部位保留的时间长于游离适体,并且比水凝胶或游离适体产生显着更高的抗肿瘤效果和存活率。此外,在用Cas9/PAH处理的肿瘤组织中观察到增加的免疫细胞过滤。

总之,这些结果表明,我们的Cas9/sgRNA编辑的免疫检查点阻断适体水凝胶具有很强的抗癌免疫治疗潜力。

原始出处:

Lee J, Le QV, et al., Cas9-edited immune checkpoint blockade PD-1 DNA polyaptamer hydrogel for cancer immunotherapy. Biomaterials. 2019 Jul 15;218:119359. doi: 10.1016/j.biomaterials.2019.119359.

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    2020-01-27 sunylz
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    2019-07-30 respect
  5. [GetPortalCommentsPageByObjectIdResponse(id=2050052, encodeId=b6ba20500529a, content=<a href='/topic/show?id=cbdd3451e3' target=_blank style='color:#2F92EE;'>#Biomaterials#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3451, encryptionId=cbdd3451e3, topicName=Biomaterials)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8e0333, createdName=zhangyxzsh, createdTime=Sat May 02 14:49:00 CST 2020, time=2020-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1918777, encodeId=75281918e778c, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Mon Jan 27 23:49:00 CST 2020, time=2020-01-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1340517, encodeId=30d8134051e6f, content=<a href='/topic/show?id=dd1a29055c8' target=_blank style='color:#2F92EE;'>#免疫检查点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29055, encryptionId=dd1a29055c8, topicName=免疫检查点)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKUdkK5dVTue7YQDvwqM1ugOuEpDZEzvXhoGClFiavehcrNAYDuPbks3MkKLPpyAEicgic80KguxwicYQ/132, createdBy=ec952500165, createdName=ms5187542471278033, createdTime=Tue Jul 30 08:49:00 CST 2019, time=2019-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1365066, encodeId=d11c1365066b8, content=<a href='/topic/show?id=3f66412ebd' target=_blank style='color:#2F92EE;'>#Cas9#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4127, encryptionId=3f66412ebd, topicName=Cas9)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8346212, createdName=respect, createdTime=Tue Jul 30 08:49:00 CST 2019, time=2019-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1615320, encodeId=715c1615320b4, content=<a href='/topic/show?id=29ae826375' target=_blank style='color:#2F92EE;'>#GRN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8263, encryptionId=29ae826375, topicName=GRN)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f68619606350, createdName=ms7517674339485982, createdTime=Tue Jul 30 08:49:00 CST 2019, time=2019-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1624929, encodeId=23011624929fc, content=<a href='/topic/show?id=0333412062' target=_blank style='color:#2F92EE;'>#Cas#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4120, encryptionId=0333412062, topicName=Cas)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=411420689333, createdName=yaanren, createdTime=Tue Jul 30 08:49:00 CST 2019, time=2019-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=370410, encodeId=8a243e04108d, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Sun Jul 28 17:52:55 CST 2019, time=2019-07-28, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=2050052, encodeId=b6ba20500529a, content=<a href='/topic/show?id=cbdd3451e3' target=_blank style='color:#2F92EE;'>#Biomaterials#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3451, encryptionId=cbdd3451e3, topicName=Biomaterials)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8e0333, createdName=zhangyxzsh, createdTime=Sat May 02 14:49:00 CST 2020, time=2020-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1918777, encodeId=75281918e778c, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Mon Jan 27 23:49:00 CST 2020, time=2020-01-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1340517, encodeId=30d8134051e6f, content=<a href='/topic/show?id=dd1a29055c8' target=_blank style='color:#2F92EE;'>#免疫检查点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29055, encryptionId=dd1a29055c8, topicName=免疫检查点)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKUdkK5dVTue7YQDvwqM1ugOuEpDZEzvXhoGClFiavehcrNAYDuPbks3MkKLPpyAEicgic80KguxwicYQ/132, createdBy=ec952500165, createdName=ms5187542471278033, createdTime=Tue Jul 30 08:49:00 CST 2019, time=2019-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1365066, encodeId=d11c1365066b8, content=<a href='/topic/show?id=3f66412ebd' target=_blank style='color:#2F92EE;'>#Cas9#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4127, encryptionId=3f66412ebd, topicName=Cas9)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8346212, createdName=respect, createdTime=Tue Jul 30 08:49:00 CST 2019, time=2019-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1615320, encodeId=715c1615320b4, content=<a href='/topic/show?id=29ae826375' target=_blank style='color:#2F92EE;'>#GRN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8263, encryptionId=29ae826375, topicName=GRN)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f68619606350, createdName=ms7517674339485982, createdTime=Tue Jul 30 08:49:00 CST 2019, time=2019-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1624929, encodeId=23011624929fc, content=<a href='/topic/show?id=0333412062' target=_blank style='color:#2F92EE;'>#Cas#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4120, encryptionId=0333412062, topicName=Cas)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=411420689333, createdName=yaanren, createdTime=Tue Jul 30 08:49:00 CST 2019, time=2019-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=370410, encodeId=8a243e04108d, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Sun Jul 28 17:52:55 CST 2019, time=2019-07-28, status=1, ipAttribution=)]
    2019-07-30 yaanren
  7. [GetPortalCommentsPageByObjectIdResponse(id=2050052, encodeId=b6ba20500529a, content=<a href='/topic/show?id=cbdd3451e3' target=_blank style='color:#2F92EE;'>#Biomaterials#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3451, encryptionId=cbdd3451e3, topicName=Biomaterials)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8e0333, createdName=zhangyxzsh, createdTime=Sat May 02 14:49:00 CST 2020, time=2020-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1918777, encodeId=75281918e778c, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Mon Jan 27 23:49:00 CST 2020, time=2020-01-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1340517, encodeId=30d8134051e6f, content=<a href='/topic/show?id=dd1a29055c8' target=_blank style='color:#2F92EE;'>#免疫检查点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29055, encryptionId=dd1a29055c8, topicName=免疫检查点)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKUdkK5dVTue7YQDvwqM1ugOuEpDZEzvXhoGClFiavehcrNAYDuPbks3MkKLPpyAEicgic80KguxwicYQ/132, createdBy=ec952500165, createdName=ms5187542471278033, createdTime=Tue Jul 30 08:49:00 CST 2019, time=2019-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1365066, encodeId=d11c1365066b8, content=<a href='/topic/show?id=3f66412ebd' target=_blank style='color:#2F92EE;'>#Cas9#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4127, encryptionId=3f66412ebd, topicName=Cas9)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8346212, createdName=respect, createdTime=Tue Jul 30 08:49:00 CST 2019, time=2019-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1615320, encodeId=715c1615320b4, content=<a href='/topic/show?id=29ae826375' target=_blank style='color:#2F92EE;'>#GRN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8263, encryptionId=29ae826375, topicName=GRN)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f68619606350, createdName=ms7517674339485982, createdTime=Tue Jul 30 08:49:00 CST 2019, time=2019-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1624929, encodeId=23011624929fc, content=<a href='/topic/show?id=0333412062' target=_blank style='color:#2F92EE;'>#Cas#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4120, encryptionId=0333412062, topicName=Cas)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=411420689333, createdName=yaanren, createdTime=Tue Jul 30 08:49:00 CST 2019, time=2019-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=370410, encodeId=8a243e04108d, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Sun Jul 28 17:52:55 CST 2019, time=2019-07-28, status=1, ipAttribution=)]
    2019-07-28 天地飞扬

    学习

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