基于合成基因线路的智能药物
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摘要
合成生物学自诞生以来对生物学领域的研究产生了重要的影响。利用工程学思维与方法,合成生物学揭开了生命系统许多调控机制,改造并扩展了一系列生物元件,同时带来了广泛的生物医学应用,为疾病诊断与治疗提供了新的思路。本文综述了适用于哺乳动物细胞或者细菌的合成基因线路并用于疾病诊断与治疗领域的最新进展,为未来智能药物设计提供新的思路。
Synthetic biology has an important impact on biology research since its birth. Applying the thought and methods that reference from electrical engineering, synthetic biology uncovers many regulatory mechanisms of life systems, transforms and expands a series of biological components. Therefore, it brings a wide range of biomedical applications, including providing new ideas for disease diagnosis and treatment. This review describes the latest advances in the field of disease diagnosis and therapy based on mammalian cell or bacterial synthetic gene circuits, and provides new ideas for future smart therapy design.
Synthetic biology has an important impact on biology research since its birth. Applying the thought and methods that reference from electrical engineering, synthetic biology uncovers many regulatory mechanisms of life systems, transforms and expands a series of biological components. Therefore, it brings a wide range of biomedical applications, including providing new ideas for disease diagnosis and treatment. This review describes the latest advances in the field of disease diagnosis and therapy based on mammalian cell or bacterial synthetic gene circuits, and provides new ideas for future smart therapy design.
引文
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[30]Polstein LR,Gersbach CA.A light-inducible CRISPR-Cas9 system for control of endogenous gene activation.Nat Chem Biol,2015,11(3):198–200.
[31]Liu YC,Zeng YY,Liu L,et al.Synthesizing AND gate genetic circuits based on CRISPR-Cas9 for identification of bladder cancer cells.Nat Commun,2014,5:5393.
[32]Liu YC,Zhan YH,Chen ZC,et al.Directing cellular information flow via CRISPR signal conductors.Nat Methods,2016,13(11):938–944.
[33]Zalatan JG,Lee ME,Almeida R,et al.Engineering complex synthetic transcriptional programs with CRISPR RNA scaffolds.Cell,2015,160(1/2):339–350.
[34]Kiani S,Chavez A,Tuttle M,et al.Cas9 g RNA engineering for genome editing,activation and repression.Nat Methods,2015,12(11):1051–1054.
[35]Ma DC,Peng SG,Xie Z.Integration and exchange of split d Cas9 domains for transcriptional controls in mammalian cells.Nat Commun,2016,7:13056.
[36]Gao YC,Xiong X,Wong S,et al.Complex transcriptional modulation with orthogonal and inducible d Cas9 regulators.Nat Methods,2016,13(12):1043–1049.
[37]Gupta S,Bram EE,Weiss R.Genetically programmable pathogen sense and destroy.ACS Synth Biol,2013,2(12):715–723.
[38]Hwang IY,Tan MH,Koh E,et al.Reprogramming microbes to be pathogen-seeking killers.ACS Synth Biol,2013,3(4):228–237.
[39]Yu B,Yang M,Shi L,et al.Explicit hypoxia targeting with tumor suppression by creating an“obligate”anaerobic Salmonella Typhimurium strain.Sci Rep,2012,2:436.
[40]Guo ZL,Yu B,Ning BT,et al.Genetically modified“obligate”anaerobic Salmonella typhimurium as a therapeutic strategy for neuroblastoma.J Hematol Oncol,2015,8:99.
[41]Shi L,Yu B,Cai CH,et al.Combined prokaryotic-eukaryotic delivery and expression of therapeutic factors through a primed autocatalytic positive-feedback loop.J Controlled Release,2016,222:130–140.
[42]Shi L,Yu B,Cai CH,et al.Angiogenic inhibitors delivered by the typeⅢsecretion system of tumor-targeting Salmonella typhimurium safely shrink tumors in mice.AMB Express,2016,6(1):56.
[43]Swofford CA,Van Dessel N,Forbes NS.Quorum-sensing Salmonella selectively trigger protein expression within tumors.Proc Natl Acad Sci USA,2015,112(11):3457–3462.
[44]Din MO,Danino T,Prindle A,et al.Synchronized cycles of bacterial lysis for in vivo delivery.Nature,2016,536(7614):81–85.
[45]Danino T,Prindle A,Kwong GA,et al.Programmable probiotics for detection of cancer in urine.Sci Transl Med,2015,7(289):289ra84.
[46]Borrero J,Chen YQ,Dunny GM,et al.Modified lactic acid bacteria detect and inhibit multiresistantenterococci.ACS Synth Biol,2015,4(3):299–306.
[47]Morel M,Shtrahman R,Rotter V,et al.Cellular heterogeneity mediates inherent sensitivity-specificity tradeoff in cancer targeting by synthetic circuits.Proc Natl Acad Sci USA,2016,113(29):8133–8138.
[48]Mishra D,Rivera PM,Lin A,et al.A load driver device for engineering modularity in biological networks.Nat Biotechnol,2014,32(12):1268–1275.
[2]Atkinson MR,Savageau MA,Myers JT,et al.Development of genetic circuitry exhibiting toggle switch or oscillatory behavior in Escherichia coli.Cell,2003,113(5):597–607.
[3]Elowitz MB,Leibler S.A synthetic oscillatory network of transcriptional regulators.Nature,2000,403(6767):335–338.
[4]Tigges M,Marquez-Lago TT,Stelling J,et al.A tunable synthetic mammalian oscillator.Nature,2009,457(7227):309–312.
[5]Basu S,Gerchman Y,Collins CH,et al.A synthetic multicellular system for programmed pattern formation.Nature,2005,434(7037):1130–1134.
[6]Liu CL,Fu XF,Liu LZ,et al.Sequential establishment of stripe patterns in an expanding cell population.Science,2011,334(6053):238–241.
[7]Xie Z,Wroblewska L,Prochazka L,et al.Multi-input RNAi-based logic circuit for identification of specific cancer cells.Science,2011,333(6047):1307–1311.
[8]Benenson Y.RNA-based computation in live cells.Curr Opin Biotechnol,2009,20(4):471–478.
[9]Davila ML,Riviere I,Wang XY,et al.Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia.Sci Transl Med,2014,6(224):224–225.
[10]Sadelain M,Rivière I,Brentjens R.Targeting tumours with genetically enhanced T lymphocytes.Nat Rev Cancer,2003,3(1):35–45.
[11]Song DG,Ye QR,Carpenito C,et al.In vivo persistence,tumor localization,and antitumor activity of CAR-engineered T cells is enhanced by costimulatory signaling through CD137(4-1BB).Cancer Res,2011,71(13):4617–4627.
[12]Savoldo B,Ramos CA,Liu EL,et al.CD28costimulation improves expansion and persistence of chimeric antigen receptor–modified T cells in lymphoma patients.J Clin Invest,2011,121(5):1822–1826.
[13]Gandhi M,Jones K.Optimizing tumor-targeting chimeric antigen receptor T cells in B-cell lymphoma patients.Immunotherapy,2011,3(12):1441–1443.
[14]Morgan RA,Yang JC,Kitano M,et al.Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2.Mol Ther,2010,18(4):843–851.
[15]De Francesco L.CAR-T cell therapy seeks strategies to harness cytokine storm.Nat Biotechnol,2014,32(7):604.
[16]Wu CY,Roybal KT,Puchner EM,et al.Remote control of therapeutic T cells through a small molecule–gated chimeric receptor.Science,2015,350(6258):aab4077.
[17]Wei P,Wong WW,Park JS,et al.Bacterial virulence proteins as tools to rewire kinase pathways in yeast and immune cells.Nature,2012,488(7411):384–388.
[18]Bray SJ.Notch signalling:a simple pathway becomes complex.Nat Rev Mol Cell Biol,2006,7(9):678–689.
[19]Morsut L,Roybal KT,Xiong X,et al.Engineering customized cell sensing and response behaviors using synthetic notch receptors.Cell,2016,164(4):780–791.
[20]Roybal KT,Rupp LJ,Morsut L,et al.Precision tumor recognition by T cells with combinatorial antigen-sensing circuits.Cell,2016,164(4):770–779.
[21]Roybal KT,Williams JZ,Morsut L,et al.Engineering T cells with customized therapeutic response programs using synthetic notch receptors.Cell,2016,167(2):419–432.e16.
[22]Li YQ,Jiang Y,Chen H,et al.Modular construction of mammalian gene circuits using TALE transcriptional repressors.Nat Chem Biol,2015,11(3):207–213.
[23]Haefliger B,Prochazka L,Angelici B,et al.Precision multidimensional assay for highthroughput micro RNA drug discovery.Nat Commun,2016,7:10709.
[24]Mali P,Yang LH,Esvelt KM,et al.RNA-guided human genome engineering via Cas9.Science,2013,339(6121):823–826.
[25]Cong L,Ran FA,Cox D,et al.Multiplex genome engineering using CRISPR/Cas systems.Science,2013,339(6121):819–823.
[26]Moore R,Spinhirne A,Lai MJ,et al.CRISPR-based self-cleaving mechanism for controllable gene delivery in human cells.Nucleic Acids Res,2015,43(2):1297–1303.
[27]Slaymaker IM,Gao LY,Zetsche B,et al.Rationally engineered Cas9 nucleases with improved specificity.Science,2016,351(6268):84–88.
[28]Kleinstiver BP,Pattanayak V,Prew MS,et al.High-fidelity CRISPR–Cas9 nucleases with no detectable genome-wide off-target effects.Nature,2016,529(7587):490–495.
[29]Davis KM,Pattanayak V,Thompson DB,et al.Small molecule-triggered Cas9 protein with improved genome-editing specificity.Nat Chem Biol,2015,11(5):316–318.
[30]Polstein LR,Gersbach CA.A light-inducible CRISPR-Cas9 system for control of endogenous gene activation.Nat Chem Biol,2015,11(3):198–200.
[31]Liu YC,Zeng YY,Liu L,et al.Synthesizing AND gate genetic circuits based on CRISPR-Cas9 for identification of bladder cancer cells.Nat Commun,2014,5:5393.
[32]Liu YC,Zhan YH,Chen ZC,et al.Directing cellular information flow via CRISPR signal conductors.Nat Methods,2016,13(11):938–944.
[33]Zalatan JG,Lee ME,Almeida R,et al.Engineering complex synthetic transcriptional programs with CRISPR RNA scaffolds.Cell,2015,160(1/2):339–350.
[34]Kiani S,Chavez A,Tuttle M,et al.Cas9 g RNA engineering for genome editing,activation and repression.Nat Methods,2015,12(11):1051–1054.
[35]Ma DC,Peng SG,Xie Z.Integration and exchange of split d Cas9 domains for transcriptional controls in mammalian cells.Nat Commun,2016,7:13056.
[36]Gao YC,Xiong X,Wong S,et al.Complex transcriptional modulation with orthogonal and inducible d Cas9 regulators.Nat Methods,2016,13(12):1043–1049.
[37]Gupta S,Bram EE,Weiss R.Genetically programmable pathogen sense and destroy.ACS Synth Biol,2013,2(12):715–723.
[38]Hwang IY,Tan MH,Koh E,et al.Reprogramming microbes to be pathogen-seeking killers.ACS Synth Biol,2013,3(4):228–237.
[39]Yu B,Yang M,Shi L,et al.Explicit hypoxia targeting with tumor suppression by creating an“obligate”anaerobic Salmonella Typhimurium strain.Sci Rep,2012,2:436.
[40]Guo ZL,Yu B,Ning BT,et al.Genetically modified“obligate”anaerobic Salmonella typhimurium as a therapeutic strategy for neuroblastoma.J Hematol Oncol,2015,8:99.
[41]Shi L,Yu B,Cai CH,et al.Combined prokaryotic-eukaryotic delivery and expression of therapeutic factors through a primed autocatalytic positive-feedback loop.J Controlled Release,2016,222:130–140.
[42]Shi L,Yu B,Cai CH,et al.Angiogenic inhibitors delivered by the typeⅢsecretion system of tumor-targeting Salmonella typhimurium safely shrink tumors in mice.AMB Express,2016,6(1):56.
[43]Swofford CA,Van Dessel N,Forbes NS.Quorum-sensing Salmonella selectively trigger protein expression within tumors.Proc Natl Acad Sci USA,2015,112(11):3457–3462.
[44]Din MO,Danino T,Prindle A,et al.Synchronized cycles of bacterial lysis for in vivo delivery.Nature,2016,536(7614):81–85.
[45]Danino T,Prindle A,Kwong GA,et al.Programmable probiotics for detection of cancer in urine.Sci Transl Med,2015,7(289):289ra84.
[46]Borrero J,Chen YQ,Dunny GM,et al.Modified lactic acid bacteria detect and inhibit multiresistantenterococci.ACS Synth Biol,2015,4(3):299–306.
[47]Morel M,Shtrahman R,Rotter V,et al.Cellular heterogeneity mediates inherent sensitivity-specificity tradeoff in cancer targeting by synthetic circuits.Proc Natl Acad Sci USA,2016,113(29):8133–8138.
[48]Mishra D,Rivera PM,Lin A,et al.A load driver device for engineering modularity in biological networks.Nat Biotechnol,2014,32(12):1268–1275.