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告别针头注射:口服胶囊mRNA疫苗要来了,灵感来自乌龟

2022-02-01 生物世界 生物世界

像大多数疫苗一样,mRNA疫苗也需要使用注射器来注射,这对于害怕针头的人来说可能是一个障碍。如果mRNA疫苗能够通过口服的方式递送,无疑能帮助人们更容易接受。

像大多数疫苗一样,mRNA疫苗也需要使用注射器来注射,这对于害怕针头的人来说可能是一个障碍。如果mRNA疫苗能够通过口服的方式递送,无疑能帮助人们更容易接受。

然而,核酸容易降解,RNA尤其容易降解,更何况是在消化道中。如果能够克服核酸在消化道中的降解难题,除了用于口服mRNA疫苗外,还可用于将RNA或DNA药物直接输送到消化道,从而更容易治疗胃肠道疾病。

2022年1月31日,麻省理工学院(MIT)的 Robert Langer 教授和 Giovanni Traverso 教授等人在 Matter 期刊发表了题为:Oral mRNA delivery using capsule-mediated gastrointestinal tissue injections 的研究论文【1】。

研究团队开发出了一种新的方法,告别针头,可以通过口服胶囊来递送mRNA疫苗,研究团队在猪上进行了实验,这种胶囊可以向猪的胃中递送多大150微克mRNA,这比mRNA新冠疫苗的使用量还要大。研究团队认为,这种mRNA的口服给药方式可以促进疫苗等间歇性干预措施的快速部署,并支持长期治疗。

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在过去几年里,Robert Langer 教授和 Giovanni Traverso 教授一直在开发将药物递送到胃肠道中的新方法。

2019年2月,他们在 Science 期刊发表了一项题为:An ingestible self-orienting system for oral delivery of macromolecules的研究论文【2】。

他们开发了一种蓝莓大小的胶囊,这种胶囊能够通过口服到达胃部后向胃壁注射胰岛素,从而降低血糖。重要的是,这种胶囊能够自我纠正方向,保证将药物准确注射到胃壁。

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胶囊的原理

在胶囊内,针头连接到压缩弹簧上,压缩弹簧由糖制成的圆盘固定就位。当吞咽胶囊时,胃中的水溶解糖圆盘,释放弹簧并将针注射到胃壁中。由于胃壁没有疼痛感受器,因此患者无法感受到注射带来的疼痛。为了确保将药物注入胃壁,研究人员设计了能够在胃中使用胶囊,针可能与胃的内壁接触。

一旦将针尖注入胃壁,胰岛素就会以制备胶囊时由研究人员控制的速率溶解。在这项研究中,所有胰岛素完全释放到血液中大约需要一个小时。

灵感来源

研究团队称这一灵感来自于一种被称为豹龟的乌龟的自我定位特征。这种乌龟是在非洲发现的,它的外壳有一个高而陡峭的圆顶,它允许自己翻滚并快速恢复正常姿态。研究团队利用计算机建模并设计了这种胶囊的外形结构,让它们在胃部的动态环境中也可以重新定位,保证注射的准确性。

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在2021年,研究团队表明,可以使用这种胶囊以液体形式递送蛋白类大分子,例如单克隆抗体。接下来,他们开始尝试使用这种胶囊来递送核酸。

众所周知,核酸进入人体后易被降解,因此需要由保护性粒子携带。LRobert Langer 教授和 Giovanni Traverso 教授最近开发的一种能够高效递送RNA的新型聚合物纳米颗粒。这种纳米颗粒由聚(β-氨基酯)制成,他们发现,这种聚合物的支化形式比线性形式更好地保护核酸并使它们进入细胞。

研究团队首先测试了这种支化聚(β-氨基酯)纳米颗粒的效果,实验结果显示,注射后,纳米颗粒携带的mRNA被递送到了胃、肝脏等器官中,并得到有效表达。

接下来,研究团队将mRNA-纳米颗粒复合物冷冻干燥,并将其包装到胶囊中。与诺和诺德的科学家合作,他们在每个胶囊中装载约50微克的mRNA,并通过口服形式一次将3个胶囊输送到猪的胃中。这一递送量超过了目前使用的mRNA新冠疫苗,mRNA新冠疫苗一次注射约有30-100微克mRNA。

图片

在对猪的研究中,研究团队发现猪的胃部细胞成功产生了报告蛋白,但其他器官和组织没有看到。研究团队表示,将在后续研究中改进纳米颗粒组成或给予更大剂量,来增加其他器官对递送进去的mRNA的吸收。研究团队还表示,也有可能仅向胃部递送mRNA就足以诱导产生强烈的免疫反应,因为胃肠道中有许多免疫细胞,刺激胃肠道的免疫系统能够产生免疫反应。

此外,研究团队还表示,这种胶囊递送mRNA的方法,除了用来递送疫苗外,还能够被用来靶向治疗胃肠道疾病。通过静脉注射或皮下注射药物,很难将核酸类药物地送到胃肠道,而这种胶囊无疑为传统方式难以治疗的胃肠道疾病开辟了新的道路。

论文链接:
https://doi.org/10.1016/j.matt.2021.12.022
http://science.sciencemag.org/content/363/6427/611

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  2. [GetPortalCommentsPageByObjectIdResponse(id=1947451, encodeId=df29194e451b9, content=<a href='/topic/show?id=88d81556543' target=_blank style='color:#2F92EE;'>#RNA疫苗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15565, encryptionId=88d81556543, topicName=RNA疫苗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=医者仁心, createdTime=Tue Sep 20 08:13:25 CST 2022, time=2022-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1197081, encodeId=b5c0119e081ef, content=🐮, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8be75220179, createdName=向药师, createdTime=Fri Feb 25 03:18:05 CST 2022, time=2022-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1189808, encodeId=ecdd118980880, content=谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210504/ce7b21bc36924fee9a17534e5d86a152/e16f85adfd25477abc351fa069229e68.jpg, createdBy=b3985491982, createdName=韩芳微萱, createdTime=Thu Feb 03 00:40:35 CST 2022, time=2022-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1189625, encodeId=f8c5118962587, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Tue Feb 01 22:44:02 CST 2022, time=2022-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1189603, encodeId=c45a11896034b, content=厉害了, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d3fa6482137, createdName=ms9000001995137444, createdTime=Tue Feb 01 21:47:58 CST 2022, time=2022-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1189599, encodeId=6d1a1189599f0, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82d31990773, createdName=robbert123, createdTime=Tue Feb 01 21:31:33 CST 2022, time=2022-02-01, status=1, ipAttribution=)]
    2022-02-25 向药师

    🐮

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1947451, encodeId=df29194e451b9, content=<a href='/topic/show?id=88d81556543' target=_blank style='color:#2F92EE;'>#RNA疫苗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15565, encryptionId=88d81556543, topicName=RNA疫苗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=医者仁心, createdTime=Tue Sep 20 08:13:25 CST 2022, time=2022-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1197081, encodeId=b5c0119e081ef, content=🐮, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8be75220179, createdName=向药师, createdTime=Fri Feb 25 03:18:05 CST 2022, time=2022-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1189808, encodeId=ecdd118980880, content=谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210504/ce7b21bc36924fee9a17534e5d86a152/e16f85adfd25477abc351fa069229e68.jpg, createdBy=b3985491982, createdName=韩芳微萱, createdTime=Thu Feb 03 00:40:35 CST 2022, time=2022-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1189625, encodeId=f8c5118962587, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Tue Feb 01 22:44:02 CST 2022, time=2022-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1189603, encodeId=c45a11896034b, content=厉害了, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d3fa6482137, createdName=ms9000001995137444, createdTime=Tue Feb 01 21:47:58 CST 2022, time=2022-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1189599, encodeId=6d1a1189599f0, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82d31990773, createdName=robbert123, createdTime=Tue Feb 01 21:31:33 CST 2022, time=2022-02-01, status=1, ipAttribution=)]
    2022-02-03 韩芳微萱

    谢谢分享!

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1947451, encodeId=df29194e451b9, content=<a href='/topic/show?id=88d81556543' target=_blank style='color:#2F92EE;'>#RNA疫苗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15565, encryptionId=88d81556543, topicName=RNA疫苗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=医者仁心, createdTime=Tue Sep 20 08:13:25 CST 2022, time=2022-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1197081, encodeId=b5c0119e081ef, content=🐮, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8be75220179, createdName=向药师, createdTime=Fri Feb 25 03:18:05 CST 2022, time=2022-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1189808, encodeId=ecdd118980880, content=谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210504/ce7b21bc36924fee9a17534e5d86a152/e16f85adfd25477abc351fa069229e68.jpg, createdBy=b3985491982, createdName=韩芳微萱, createdTime=Thu Feb 03 00:40:35 CST 2022, time=2022-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1189625, encodeId=f8c5118962587, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Tue Feb 01 22:44:02 CST 2022, time=2022-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1189603, encodeId=c45a11896034b, content=厉害了, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d3fa6482137, createdName=ms9000001995137444, createdTime=Tue Feb 01 21:47:58 CST 2022, time=2022-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1189599, encodeId=6d1a1189599f0, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82d31990773, createdName=robbert123, createdTime=Tue Feb 01 21:31:33 CST 2022, time=2022-02-01, status=1, ipAttribution=)]
    2022-02-01 1209e435m98(暂无昵称)

    学习了,谢谢分享

    0

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    2022-02-01 ms9000001995137444

    厉害了

    0

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    2022-02-01 robbert123

    学习

    0

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