Challenges and progress of neurodrug: bioactivities, production and delivery strategies of nerve growth factor protein.

IF 5.7 3区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Journal of Biological Engineering Pub Date : 2023-12-04 DOI:10.1186/s13036-023-00392-2
Nan Zhou, TingWei Gu, Yang Xu, Yuda Liu, LiHua Peng
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Abstract

Nerve growth factor (NGF) is a vital cytokine that plays a crucial role in the development and regeneration of the nervous system. It has been extensively studied for its potential therapeutic applications in various neural diseases. However, as a protein drug, limited natural source seriously hinders its translation and clinical applications. Conventional extraction of NGF from mouse submandibular glands has a very high cost and potentially induces immunogenicity; total synthesis and semi-synthesis methods are alternatives, but have difficulty in obtaining correct protein structure; gene engineering of plant cells is thought to be non-immunogenic, bioactive and economical. Meanwhile, large molecular weight, high polarity, and negative electrical charge make it difficult for NGF to cross the blood brain barrier to reach therapeutic targets. Current delivery strategies mainly depend on the adenovirus and cell biodelivery, but the safety and efficacy remain to be improved. New materials are widely investigated for the controllable, safe and precise delivery of NGF. This review illustrates physiological and therapeutic effects of NGF for various diseases. Moreover, new progress in production and delivery technologies for NGF are summarized. Bottlenecks encountered in the development of NGF as therapeutics are also discussed with the countermeasures proposed.

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神经药物的挑战与进展:神经生长因子蛋白的生物活性、生产和递送策略。
神经生长因子(NGF)是一种重要的细胞因子,对神经系统的发育和再生起着至关重要的作用。由于其在各种神经疾病中的潜在治疗应用,已被广泛研究。然而,作为一种蛋白质药物,天然来源有限严重阻碍了其转化和临床应用。从小鼠颌下腺中提取NGF的传统方法成本很高,并且可能诱导免疫原性;全合成法和半合成法是替代方法,但难以获得正确的蛋白质结构;植物细胞基因工程被认为具有非免疫原性、生物活性和经济性。同时,NGF的大分子量、高极性和负电荷使其难以通过血脑屏障到达治疗靶点。目前的递送策略主要依赖于腺病毒和细胞生物递送,但安全性和有效性有待提高。为了实现NGF的可控、安全、精确输送,人们正在广泛研究新材料。本文就神经生长因子在多种疾病中的生理和治疗作用作一综述。综述了NGF生产和输送技术的最新进展。本文还讨论了神经生长因子作为治疗药物发展中遇到的瓶颈,并提出了相应的对策。
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来源期刊
Journal of Biological Engineering
Journal of Biological Engineering BIOCHEMICAL RESEARCH METHODS-BIOTECHNOLOGY & APPLIED MICROBIOLOGY
CiteScore
7.10
自引率
1.80%
发文量
32
审稿时长
17 weeks
期刊介绍: Biological engineering is an emerging discipline that encompasses engineering theory and practice connected to and derived from the science of biology, just as mechanical engineering and electrical engineering are rooted in physics and chemical engineering in chemistry. Topical areas include, but are not limited to: Synthetic biology and cellular design Biomolecular, cellular and tissue engineering Bioproduction and metabolic engineering Biosensors Ecological and environmental engineering Biological engineering education and the biodesign process As the official journal of the Institute of Biological Engineering, Journal of Biological Engineering provides a home for the continuum from biological information science, molecules and cells, product formation, wastes and remediation, and educational advances in curriculum content and pedagogy at the undergraduate and graduate-levels. Manuscripts should explore commonalities with other fields of application by providing some discussion of the broader context of the work and how it connects to other areas within the field.
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