Baidu
map

血液科

订阅

MedSci主页 / 所有栏目 / 血液科

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
关注

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.

版权声明：
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料，版权均属于梅斯医学所有。非经授权，任何媒体、网站或个人不得转载，授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章，或“梅斯号”自媒体发布的文章，仅系出于传递更多信息之目的，本站仅负责审核内容合规，其内容不代表本站立场，本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系，我们将立即进行删除处理。
在此留言
评论区 (4)
#插入话题
  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=80, 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=78, 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=84, 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=79, 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=80, 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=78, 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=84, 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=79, 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=80, 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=78, 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=84, 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=79, 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=80, 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=78, 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=84, 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=79, 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

相关资讯

Blood：EPCR缺陷或EPCR抗体可预防血友病性关节病

EPCR缺陷可通过减少关节出血预防血友病性关节病。 单剂量EPCR封闭抗体可减轻血友病性关节病的进展。

Blood：评估Emicizumab功能的新模型！

艾米珠单抗 (≥1.5 mg/kg)可部分纠正A型血友病出血模型中的失血，FVIII等效值为9 U/d。 当与低剂量的凝血因子VIII一起使用时，艾米珠单抗可提供附加的止血活性。

2019 UKHCDO指南：艾美赛珠单抗治疗与实验室凝血检测

2019年12月，英国血友病中心医师组织(UKHCDO)发布了艾美赛珠单抗治疗与实验室凝血检测指南，VIII因子类似物艾美赛珠单抗有一种新型作用方式影响了接种这种药物治疗患者的实验室检测结果。本文主要针对接受艾美赛珠单抗治疗的血友病A患者应用合适的实验室分析的应用提供指导建议。

专家：儿童期是血友病治疗的关键时期 应及早采取规范化预防治疗

专家17日在北京血友之家罕见病关爱中心主办的公众教育活动中强调，儿童期是血友病治疗的关键时期，应及早采取规范化预防治疗，提前干预有利于儿童的关节发育，减轻出血症状，减少致残率。

辉瑞TFPI抗体Marstacimab用于血友病治疗，在国内将开展临床试验

5月16日，辉瑞TFPI（组织因子途径抑制物）抗体药物Marstacimab申报临床获得CDE受理。Marstacimab是首个在中国申报临床的TFPI抗体。常见的血友病为A型（缺乏FVⅢ）和B型（缺

有关KO血友病的药物问世：基因治疗药物Valrox有望上市

甲型血友病，也称凝血因子八（FVIII）缺乏症，以凝血因子VIII缺失或缺陷引起的遗传性疾病，目前缺少根本治疗手段。据美国疾病预防控制中心（CDC）的报道，在美国，每5,000例活产胎儿中就有1例胎儿患有该病，血友病患者总数约为20,000人。据全球血友病发病率的准确数据，估计全球有超过40万的血友病患者。重症甲型血友病患者经常会发生自发性且疼痛的肌肉或关节部位的出血，该人群约占甲型血友病患者总数

Baidu
map
Baidu
map
Baidu
map