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Blood：AAV5基因治疗后人血浆中转基因产生的VIII因子的活性

2020-10-05 星云 MedSci原创

血友病基因治疗FVIII活性
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以腺相关病毒(AAV)为基础的基因治疗可以恢复血友病A(HA)内源性因子VIII(FVIII)的表达。AAV载体通常利用B结构域缺失的FVIII转基因中的人FVIII-SQ。

以腺相关病毒(AAV)为基础的基因治疗可以恢复血友病A(HA)内源性因子VIII(FVIII)的表达。AAV载体通常利用B结构域缺失的FVIII转基因，如valoccogene roxparvovec(AAV5-FVIII-SQ)中的人FVIII-SQ。

两个独立试验的FVIII活性

令人惊讶的是，转基因产生的FVIII-SQ在一期血凝块(OS)中的活性是发色底物(CS)的1.3-2.0倍，而重组FVIII-SQ的OS活性低于CS。在CS实验中，转基因FVIII-SQ与重组FVIII-SQ具有相似的特异活性(IU/mg)，说明在OS实验中出现了不同的活性。

健康供体FVIII活性

不同的检测试剂盒和临床实验室中观察到转基因产生的FVIII-SQ具有较高的OS活性，这表明内在的分子特征是潜在的根本原因。在两名受试者中的进一步实验表明，转基因产生的FVIII-SQ加速了早期因子Xa和凝血酶的形成，这可能解释了较高的OS活性是基于OS和CS检测读出时间之间的动力学偏差。

尽管凝血开始较快，但凝血酶整体水平没有受到影响。与关节出血的相关性表明，OS和CS检测对于区分血友病和非血友病FVIII活性水平仍然具有临床意义。

在临床开发期间，CS活性被选为替代终点，以保守地评估止血效果，并能够与重组FVIII-SQ产品进行比较。

原始出处：

Steffen Rosen, et al. Activity of Transgene-Produced B-Domain Deleted Factor VIII in Human Plasma Following AAV5 Gene Therapy. Blood. September，2020.

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  1. [GetPortalCommentsPageByObjectIdResponse(id=1668834, encodeId=81a8166883446, content=<a href='/topic/show?id=fdea18432f3' target=_blank style='color:#2F92EE;'>#VIII因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18432, encryptionId=fdea18432f3, topicName=VIII因子)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=aa4f26457969, createdName=liye789132260, createdTime=Mon Mar 22 04:44:44 CST 2021, time=2021-03-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1916347, encodeId=4241191634e05, content=<a href='/topic/show?id=c5a89550ff' target=_blank style='color:#2F92EE;'>#III#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9550, encryptionId=c5a89550ff, topicName=III)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e68e415, createdName=juliusluan78, createdTime=Thu Apr 22 08:44:44 CST 2021, time=2021-04-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1271873, encodeId=7fd412e1873b0, content=<a href='/topic/show?id=9fef169483' target=_blank style='color:#2F92EE;'>#AAV#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1694, encryptionId=9fef169483, topicName=AAV)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8ba7103, createdName=xuqianhua, createdTime=Wed Oct 07 02:44:44 CST 2020, time=2020-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1471928, encodeId=7dcc14e1928c8, content=<a href='/topic/show?id=e97a93305ec' target=_blank style='color:#2F92EE;'>#转基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93305, encryptionId=e97a93305ec, topicName=转基因)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=76227191338, createdName=旅苦化文_210, createdTime=Wed Oct 07 02:44:44 CST 2020, time=2020-10-07, status=1, ipAttribution=)]
    2021-03-22 liye789132260

    #VIII因子#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1668834, encodeId=81a8166883446, content=<a href='/topic/show?id=fdea18432f3' target=_blank style='color:#2F92EE;'>#VIII因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18432, encryptionId=fdea18432f3, topicName=VIII因子)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=aa4f26457969, createdName=liye789132260, createdTime=Mon Mar 22 04:44:44 CST 2021, time=2021-03-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1916347, encodeId=4241191634e05, content=<a href='/topic/show?id=c5a89550ff' target=_blank style='color:#2F92EE;'>#III#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9550, encryptionId=c5a89550ff, topicName=III)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e68e415, createdName=juliusluan78, createdTime=Thu Apr 22 08:44:44 CST 2021, time=2021-04-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1271873, encodeId=7fd412e1873b0, content=<a href='/topic/show?id=9fef169483' target=_blank style='color:#2F92EE;'>#AAV#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1694, encryptionId=9fef169483, topicName=AAV)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8ba7103, createdName=xuqianhua, createdTime=Wed Oct 07 02:44:44 CST 2020, time=2020-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1471928, encodeId=7dcc14e1928c8, content=<a href='/topic/show?id=e97a93305ec' target=_blank style='color:#2F92EE;'>#转基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93305, encryptionId=e97a93305ec, topicName=转基因)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=76227191338, createdName=旅苦化文_210, createdTime=Wed Oct 07 02:44:44 CST 2020, time=2020-10-07, status=1, ipAttribution=)]
    2021-04-22 juliusluan78

    #III#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1668834, encodeId=81a8166883446, content=<a href='/topic/show?id=fdea18432f3' target=_blank style='color:#2F92EE;'>#VIII因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18432, encryptionId=fdea18432f3, topicName=VIII因子)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=aa4f26457969, createdName=liye789132260, createdTime=Mon Mar 22 04:44:44 CST 2021, time=2021-03-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1916347, encodeId=4241191634e05, content=<a href='/topic/show?id=c5a89550ff' target=_blank style='color:#2F92EE;'>#III#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9550, encryptionId=c5a89550ff, topicName=III)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e68e415, createdName=juliusluan78, createdTime=Thu Apr 22 08:44:44 CST 2021, time=2021-04-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1271873, encodeId=7fd412e1873b0, content=<a href='/topic/show?id=9fef169483' target=_blank style='color:#2F92EE;'>#AAV#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1694, encryptionId=9fef169483, topicName=AAV)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8ba7103, createdName=xuqianhua, createdTime=Wed Oct 07 02:44:44 CST 2020, time=2020-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1471928, encodeId=7dcc14e1928c8, content=<a href='/topic/show?id=e97a93305ec' target=_blank style='color:#2F92EE;'>#转基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93305, encryptionId=e97a93305ec, topicName=转基因)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=76227191338, createdName=旅苦化文_210, createdTime=Wed Oct 07 02:44:44 CST 2020, time=2020-10-07, status=1, ipAttribution=)]
    2020-10-07 xuqianhua

    #AAV#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1668834, encodeId=81a8166883446, content=<a href='/topic/show?id=fdea18432f3' target=_blank style='color:#2F92EE;'>#VIII因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18432, encryptionId=fdea18432f3, topicName=VIII因子)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=aa4f26457969, createdName=liye789132260, createdTime=Mon Mar 22 04:44:44 CST 2021, time=2021-03-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1916347, encodeId=4241191634e05, content=<a href='/topic/show?id=c5a89550ff' target=_blank style='color:#2F92EE;'>#III#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9550, encryptionId=c5a89550ff, topicName=III)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e68e415, createdName=juliusluan78, createdTime=Thu Apr 22 08:44:44 CST 2021, time=2021-04-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1271873, encodeId=7fd412e1873b0, content=<a href='/topic/show?id=9fef169483' target=_blank style='color:#2F92EE;'>#AAV#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1694, encryptionId=9fef169483, topicName=AAV)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8ba7103, createdName=xuqianhua, createdTime=Wed Oct 07 02:44:44 CST 2020, time=2020-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1471928, encodeId=7dcc14e1928c8, content=<a href='/topic/show?id=e97a93305ec' target=_blank style='color:#2F92EE;'>#转基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93305, encryptionId=e97a93305ec, topicName=转基因)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=76227191338, createdName=旅苦化文_210, createdTime=Wed Oct 07 02:44:44 CST 2020, time=2020-10-07, status=1, ipAttribution=)]
    2020-10-07 旅苦化文_210

    #转基因#

    0

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