Non-small-molecule therapeutics for drug addiction: From pharmaco-kinetics modulating to synthetic biology

Drug addiction is a pervasive problem worldwide. It not only affects the abuser's life, but also poses a serious threat to public health. Accordingly, there is a strong demand for the development of novel and effective therapies for drug addiction. Considering that small-molecule drugs have onl...

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Main Authors: Yuanpeng Li, Yibo Wang, Lin Lu, Jie Shi, Xiaohui Wang
Format: Article
Language:English
Published: KeAi Communications Co. Ltd. 2024-11-01
Series:Fundamental Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667325822004137
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author Yuanpeng Li
Yibo Wang
Lin Lu
Jie Shi
Xiaohui Wang
author_facet Yuanpeng Li
Yibo Wang
Lin Lu
Jie Shi
Xiaohui Wang
author_sort Yuanpeng Li
collection DOAJ
description Drug addiction is a pervasive problem worldwide. It not only affects the abuser's life, but also poses a serious threat to public health. Accordingly, there is a strong demand for the development of novel and effective therapies for drug addiction. Considering that small-molecule drugs have only had limited success, there is great interest in developing alternative strategies that extend the reach of small-molecule-based therapies. The antibody-based trapping approach and the enzyme catalytic strategy have been considered as promising ways to reduce the euphoria of drug users by altering drug pharmacokinetics and decreasing drug concentrations in the central nervous system. However, these biological macromolecules are generally unstable and their in vivo half-lives are short. With the rapid development of gene editing technologies, it is possible to perform ex vivo gene therapy for the long-term and stable delivery of enzymes and other effector proteins, which could free abusers from frequent injections of therapeutics. By constructing programmed gene switches that regulate spatiotemporal gene expression in response to illicit drugs, this perspective proposed the concept of preventing drug addiction by the drug itself. This strategy enables the controlled release of therapeutic proteins in vivo and is expected to improve patient safety and compliance. This will open up new opportunities for next-generation medicine and hold great promise for expanding our ability to treat drug addiction.
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spelling doaj-art-729f6cb1e75d4c70aae3e31120ffb7612024-12-01T05:08:46ZengKeAi Communications Co. Ltd.Fundamental Research2667-32582024-11-014613981400Non-small-molecule therapeutics for drug addiction: From pharmaco-kinetics modulating to synthetic biologyYuanpeng Li0Yibo Wang1Lin Lu2Jie Shi3Xiaohui Wang4Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, ChinaLaboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, ChinaInstitute of Mental Health, Peking University Sixth Hospital and National Clinical Research Center for Mental Disorders, Peking University, Beijing 100191, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100191, China; International Data Group/McGovern Institute for Brain Research at Peking University, Peking University, Beijing 100191, ChinaNational Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing 100191, China; Corresponding authors.Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China; Beijing National Laboratory for Molecular Sciences, Beijing 100190, China; Corresponding authors.Drug addiction is a pervasive problem worldwide. It not only affects the abuser's life, but also poses a serious threat to public health. Accordingly, there is a strong demand for the development of novel and effective therapies for drug addiction. Considering that small-molecule drugs have only had limited success, there is great interest in developing alternative strategies that extend the reach of small-molecule-based therapies. The antibody-based trapping approach and the enzyme catalytic strategy have been considered as promising ways to reduce the euphoria of drug users by altering drug pharmacokinetics and decreasing drug concentrations in the central nervous system. However, these biological macromolecules are generally unstable and their in vivo half-lives are short. With the rapid development of gene editing technologies, it is possible to perform ex vivo gene therapy for the long-term and stable delivery of enzymes and other effector proteins, which could free abusers from frequent injections of therapeutics. By constructing programmed gene switches that regulate spatiotemporal gene expression in response to illicit drugs, this perspective proposed the concept of preventing drug addiction by the drug itself. This strategy enables the controlled release of therapeutic proteins in vivo and is expected to improve patient safety and compliance. This will open up new opportunities for next-generation medicine and hold great promise for expanding our ability to treat drug addiction.http://www.sciencedirect.com/science/article/pii/S2667325822004137Drug abuseEnzymatic degradationGene therapySynthetic biologyPharmacokinetics
spellingShingle Yuanpeng Li
Yibo Wang
Lin Lu
Jie Shi
Xiaohui Wang
Non-small-molecule therapeutics for drug addiction: From pharmaco-kinetics modulating to synthetic biology
Fundamental Research
Drug abuse
Enzymatic degradation
Gene therapy
Synthetic biology
Pharmacokinetics
title Non-small-molecule therapeutics for drug addiction: From pharmaco-kinetics modulating to synthetic biology
title_full Non-small-molecule therapeutics for drug addiction: From pharmaco-kinetics modulating to synthetic biology
title_fullStr Non-small-molecule therapeutics for drug addiction: From pharmaco-kinetics modulating to synthetic biology
title_full_unstemmed Non-small-molecule therapeutics for drug addiction: From pharmaco-kinetics modulating to synthetic biology
title_short Non-small-molecule therapeutics for drug addiction: From pharmaco-kinetics modulating to synthetic biology
title_sort non small molecule therapeutics for drug addiction from pharmaco kinetics modulating to synthetic biology
topic Drug abuse
Enzymatic degradation
Gene therapy
Synthetic biology
Pharmacokinetics
url http://www.sciencedirect.com/science/article/pii/S2667325822004137
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AT jieshi nonsmallmoleculetherapeuticsfordrugaddictionfrompharmacokineticsmodulatingtosyntheticbiology
AT xiaohuiwang nonsmallmoleculetherapeuticsfordrugaddictionfrompharmacokineticsmodulatingtosyntheticbiology