DEVELOPMENT OF AN ORAL CARRIER

这项研究的长期目标是开发一种新的 创造可以通过口服途径给药的药物的策略。 该策略将利用一种天然存在的物质， 肉毒杆菌毒素，它是导致 肉毒杆菌中毒 在正常情况下，这种毒素是通过 在食物中毒的时候。 摄入的毒素从肠道中逃逸 到达大气循环，从这里它被分配到 全身脆弱的细胞。 最近，两名 关于肉毒杆菌毒素已经有了一些发现。 首先是毒素 与肠细胞结合并通过肠细胞转运。 这可能是 毒素逃逸胃肠道系统的机制 达到一般循环。 第二，分子生物学技术 生物学可以用来制造一种经过改良的毒素， 保留了从肠道中逃脱的能力，但失去了 毒细胞 这种毒素的改良版本已被证明是 预防肉毒杆菌中毒的口服疫苗建议的具体目标 研究是为了测试改良的肉毒杆菌毒素 作为一种载体，将药物从肠道运输到全身， 流通 这一具体目标将通过以下三个方面来实现： 相关研究领域。 首先，分子生物学技术 将用于表达肉毒杆菌毒素的多肽片段， 可以作为载体。 接下来，将对以下动物进行体内实验： 实验室动物，以确保潜在的携带者实际上运输 药物从胃肠道系统到全身循环。 最后，将在培养的人类肠道细胞上进行体外实验 以确定携带者是否可能在人类患者中起作用。 如果运营商战略成功，它可以应用于 研制了几种口服疫苗。 此外，有可能的是， 对于每种疫苗，肽载体（即，修饰的重组 肉毒杆菌毒素）和肽抗原（即，重组疫苗） 可以作为单个嵌合基因的表达产物产生。

The long-term objective of the proposed research is to develop a novel strategy for creating drugs that can be administered by the oral route. This strategy will utilize a naturally occurring substance known as botulinum toxin, which is the etiologic agent responsible for the disease botulism. Under normal circumstances, this toxin is ingested during episodes of food poisoning. Ingested toxin escapes from the gut to reach the general circulation, and from here it is distributed to vulnerable cells throughout the body. In the recent past, two discoveries have been made about botulinum toxin. First, the toxin binds to, and is transported across, gut cells. This may be the mechanism by which the toxin escapes the gastrointestinal system to reach the general circulation. Second, the techniques of molecular biology can be used to create a modified version of the toxin that retains the ability to escape from the gut but has lost the ability to poison cells. This modified version of the toxin has been shown to be an oral vaccine against botulism. The specific aim of the proposed research is to test the possibility that modified botulinum toxin can be used as a carrier to transport drugs from the gut to the general circulation. This specific aim will be accomplished by pursuing three related areas of research. First, the techniques of molecular biology will be used to express polypeptide fragments of botulinum toxin that can act as carriers. Next, in vivo experiments will be done on laboratory animals to ensure that potential carriers actually transport drugs from the gastrointestinal system to the general circulation. Finally, in vitro experiments will be done on human gut cells in culture to determine whether the carriers are likely to act in human patients. If the carrier strategy is successful, it could be applied to the creation of several oral vaccines. Furthermore, it may be possible that for each vaccine the peptide carrier (viz., modified recombinant botulinum toxin) and the peptide antigen (viz., recombinant vaccine) could be generated as the expression product of a single chimeric gene.