活体生物药的应用及在遗传性代谢缺陷病治疗中的展望

Application of live biotherapeutic products and perspective in the treatment of inherited metabolic disease

活体生物药(live biotherapeutic products,LBPs)是指来自于人体肠道内或自然界中能够治疗人类疾病的活性菌。但天然筛选的活菌存在治疗效果不明显、差异性较大等缺点,难以满足个性化诊疗的需要。近年来,随着合成生物学的发展,研究者利用生命科学及工程科学手段,设计并构建了若干可响应外界复杂环境信号的工程菌株,加快了活体生物药的研发和应用过程。遗传性代谢缺陷病(inherited metabolic disease)是因体内某些酶的遗传缺陷致使体内相应的代谢物不能正常代谢而引发一系列临床症状的一类疾病,因此利用合成生物学技术,针对特定缺陷的酶设计重组活体生物药,未来有希望用于遗传性代谢缺陷病的治疗。本综述以活体生物药为切入点,并结合国内外文献综述,来探讨活体生物药在疾病治疗中的应用,以及对遗传性代谢缺陷病治疗的潜力。

Live biotherapeutic products(LBPs)refer to the living bacteria derived from human body intestinal gut or in nature that can be used to treat the human disease.However,the naturally screened living bacteria have some disadvantages,such as deficient therapeutic effect and great divergence,which fall short of the personalized diagnosis and treatment needs.In recent years,with the development of synthetic biology,researchers have designed and constructed several engineered strains that can respond to external complex environmental signals,which speeded up the process of development and application of LBPs.Recombinant LBPs modified by gene editing can have therapeutic effect on specific diseases.Inherited metabolic disease is a type of disease that causes a series of clinical symptoms due to the genetic defect of some enzymes in the body,which may cause abnormal metabolism the corresponding metabolites.Therefore,the use of synthetic biology to design LBPs targeting specific defective enzymes will be promising for the treatment of inherited metabolic defects in the future.This review summarizes the clinic applications of LBPs and its potential for the treatment of inherited metabolic defects.