ACS Synthetic Biology最新文献

{"title":"Macroscopic Assembly of Materials with Engineered Bacterial Spores via Coiled-Coil Interaction.","authors":"Lucas Korbanka, Ju-An Kim, Seunghyun Sim","doi":"10.1021/acssynbio.4c00468","DOIUrl":"https://doi.org/10.1021/acssynbio.4c00468","url":null,"abstract":"<p><p>Herein, we report macroscopic materials formed by the assembly of engineered bacterial spores. Spores were engineered by using a T7-driven expression system to display a high density of pH-responsive self-associating proteins on their surface. The engineered surface protein on the spore surface enabled pH-dependent binding at the protein level and enabled the assembly of granular materials. Mechanical properties remained largely constant with changing pH, but erosion stability was pH-dependent in a manner consistent with the pH-dependent interaction between the engineered surface proteins. Our finding utilizes synthetic biology for the design of macroscopic materials and illuminates the impact of coiled-coil interaction across various length scales.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fine-Regulating the Carbon Flux of l-Isoleucine Producing Corynebacterium glutamicum WM001 for Efficient l-Threonine Production","authors":"Guihong Zhao,&nbsp;Dezhi Zhang,&nbsp;Benzheng Zhou,&nbsp;Zihan Li,&nbsp;Geer Liu,&nbsp;Hedan Li,&nbsp;Xiaoqing Hu and Xiaoyuan Wang*,&nbsp;","doi":"10.1021/acssynbio.4c0051810.1021/acssynbio.4c00518","DOIUrl":"https://doi.org/10.1021/acssynbio.4c00518https://doi.org/10.1021/acssynbio.4c00518","url":null,"abstract":"<p ><span>l</span>-Threonine, an essential amino acid, is widely used in various industries, with an annually growing demand. However, the present <i>Corynebacterium glutamicum</i> strains are difficult to achieve industrialization of <span>l</span>-threonine due to low yield and purity. In this study, we engineered an <span>l</span>-isoleucine-producing <i>C. glutamicum</i> WM001 to efficiently produce <span>l</span>-threonine by finely regulating the carbon flux. First, the threonine dehydratase in WM001 was mutated to lower the level of <span>l</span>-isoleucine production, then the homoserine dehydrogenase and aspartate kinase were mutated to release the feedback inhibition of <span>l</span>-threonine, and the resulting strain TWZ006 produced 14.2 g/L <span>l</span>-threonine. Subsequently, aspartate ammonia-lyase and aspartate transaminase were overexpressed to accumulate the precursor <span>l</span>-aspartate. Next, phosphoenolpyruvate carboxylase, pyruvate carboxylase and pyruvate kinase were overexpressed, and phosphoenolpyruvate carboxykinase, oxaloacetate decarboxylase were inactivated to fine-regulate the carbon flux among oxaloacetate, pyruvate and phosphoenolpyruvate. The resulting strain TWZ017 produced 21.5 g/L <span>l</span>-threonine. Finally, dihydrodipicolinate synthase was mutated with strong allosteric inhibition from <span>l</span>-lysine to significantly decrease byproducts accumulation, <span>l</span>-threonine export was optimized, and the final engineered strain TWZ024/pXTuf-<i>thrE</i> produced 78.3 g/L of <span>l</span>-threonine with the yield of 0.33 g/g glucose and the productivity of 0.82 g/L/h in a 7 L bioreactor. To the best of our knowledge, this represents the highest <span>l</span>-threonine production in <i>C. glutamicum</i>, providing possibilities for industrial-scale production.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142450525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fine-Regulating the Carbon Flux of l-Isoleucine Producing <i>Corynebacterium glutamicum</i> WM001 for Efficient l-Threonine Production.","authors":"Guihong Zhao, Dezhi Zhang, Benzheng Zhou, Zihan Li, Geer Liu, Hedan Li, Xiaoqing Hu, Xiaoyuan Wang","doi":"10.1021/acssynbio.4c00518","DOIUrl":"https://doi.org/10.1021/acssynbio.4c00518","url":null,"abstract":"<p><p>l-Threonine, an essential amino acid, is widely used in various industries, with an annually growing demand. However, the present <i>Corynebacterium glutamicum</i> strains are difficult to achieve industrialization of l-threonine due to low yield and purity. In this study, we engineered an l-isoleucine-producing <i>C. glutamicum</i> WM001 to efficiently produce l-threonine by finely regulating the carbon flux. First, the threonine dehydratase in WM001 was mutated to lower the level of l-isoleucine production, then the homoserine dehydrogenase and aspartate kinase were mutated to release the feedback inhibition of l-threonine, and the resulting strain TWZ006 produced 14.2 g/L l-threonine. Subsequently, aspartate ammonia-lyase and aspartate transaminase were overexpressed to accumulate the precursor l-aspartate. Next, phosphoenolpyruvate carboxylase, pyruvate carboxylase and pyruvate kinase were overexpressed, and phosphoenolpyruvate carboxykinase, oxaloacetate decarboxylase were inactivated to fine-regulate the carbon flux among oxaloacetate, pyruvate and phosphoenolpyruvate. The resulting strain TWZ017 produced 21.5 g/L l-threonine. Finally, dihydrodipicolinate synthase was mutated with strong allosteric inhibition from l-lysine to significantly decrease byproducts accumulation, l-threonine export was optimized, and the final engineered strain TWZ024/pXTuf-<i>thrE</i> produced 78.3 g/L of l-threonine with the yield of 0.33 g/g glucose and the productivity of 0.82 g/L/h in a 7 L bioreactor. To the best of our knowledge, this represents the highest l-threonine production in <i>C. glutamicum</i>, providing possibilities for industrial-scale production.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing and Engineering Rhamnose-Inducible Regulatory Systems for Dynamic Control of Metabolic Pathways in Streptomyces","authors":"Qian Yang,&nbsp;Mengao Luan,&nbsp;Meiyan Wang,&nbsp;Yuxin Zhang,&nbsp;Guoqiang Liu and Guoqing Niu*,&nbsp;","doi":"10.1021/acssynbio.4c0062610.1021/acssynbio.4c00626","DOIUrl":"https://doi.org/10.1021/acssynbio.4c00626https://doi.org/10.1021/acssynbio.4c00626","url":null,"abstract":"<p >Fine-tuning gene expression is of great interest for synthetic biotechnological applications. This is particularly true for the genus <i>Streptomyces</i>, which is well-known as a prolific producer of diverse natural products. Currently, there is an increasing demand to develop effective gene induction systems. In this study, bioinformatic analysis revealed a putative rhamnose catabolic pathway in multiple <i>Streptomyces</i> species, and the removal of the pathway in the model organism <i>Streptomyces coelicolor</i> impaired its growth on minimal media with rhamnose as the sole carbon source. To unravel the regulatory mechanism of RhaR, a LacI family transcriptional regulator of the catabolic pathway, electrophoretic mobility shift assays (EMSAs) were performed to identify potential target promoters. Multiple sequence alignments retrieved a consensus sequence of the RhaR operator (<i>rhaO</i>). A synthetic biology-based strategy was then deployed to build rhamnose-inducible regulatory systems, referred to as <i>rhaRS1</i> and <i>rhaRS2</i>, by assembling the repressor/operator pair RhaR/<i>rhaO</i> with the well-defined constitutive <i>kasO*</i> promoter. Both <i>rhaRS1</i> and <i>rhaRS2</i> exhibited a high level of induced reporter activity, with no leaky expression. <i>rhaRS2</i> has been proven successful for the programmable production of actinorhodin and violacein in <i>Streptomyces</i>. Our study expanded the toolkit of inducible regulatory systems that will be broadly applicable to many other <i>Streptomyces</i> species.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142450868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing a CRISPR-Cas13d Gene Circuit for Tunable Target RNA Downregulation with Minimal Collateral RNA Cutting.","authors":"Yiming Wan, Christopher Helenek, Damiano Coraci, Gábor Balázsi","doi":"10.1021/acssynbio.4c00271","DOIUrl":"https://doi.org/10.1021/acssynbio.4c00271","url":null,"abstract":"<p><p>The invention of RNA-guided DNA cutting systems has revolutionized biotechnology. More recently, RNA-guided RNA cutting by Cas13d entered the scene as a highly promising alternative to RNA interference to engineer cellular transcriptomes for biotechnological and therapeutic purposes. Unfortunately, \"collateral damage\" by indiscriminate off-target cutting tampered enthusiasm for these systems. Yet, how collateral activity, or even RNA target reduction depends on Cas13d and guide RNA abundance has remained unclear due to the lack of expression-tuning studies to address this question. Here we use precise expression-tuning gene circuits to show that both nonspecific and specific, on-target RNA reduction depend on Cas13d and guide RNA levels, and that nonspecific RNA cutting from <i>trans</i> cleavage might contribute to on-target RNA reduction. Using RNA-level control techniques, we develop new <i>Multi-Level Optimized Negative-Autoregulated Cas13d and crRNA Hybrid</i> (MONARCH) gene circuits that achieve a high dynamic range with low basal on-target RNA reduction while minimizing collateral activity in human kidney cells and green monkey cells most frequently used in human virology. MONARCH should bring RNA-guided RNA cutting systems to the forefront, as easily applicable, programmable tools for transcriptome engineering in biotechnological and medical applications.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing a CRISPR-Cas13d Gene Circuit for Tunable Target RNA Downregulation with Minimal Collateral RNA Cutting","authors":"Yiming Wan,&nbsp;Christopher Helenek,&nbsp;Damiano Coraci and Gábor Balázsi*,&nbsp;","doi":"10.1021/acssynbio.4c0027110.1021/acssynbio.4c00271","DOIUrl":"https://doi.org/10.1021/acssynbio.4c00271https://doi.org/10.1021/acssynbio.4c00271","url":null,"abstract":"<p >The invention of RNA-guided DNA cutting systems has revolutionized biotechnology. More recently, RNA-guided RNA cutting by Cas13d entered the scene as a highly promising alternative to RNA interference to engineer cellular transcriptomes for biotechnological and therapeutic purposes. Unfortunately, “collateral damage” by indiscriminate off-target cutting tampered enthusiasm for these systems. Yet, how collateral activity, or even RNA target reduction depends on Cas13d and guide RNA abundance has remained unclear due to the lack of expression-tuning studies to address this question. Here we use precise expression-tuning gene circuits to show that both nonspecific and specific, on-target RNA reduction depend on Cas13d and guide RNA levels, and that nonspecific RNA cutting from <i>trans</i> cleavage might contribute to on-target RNA reduction. Using RNA-level control techniques, we develop new <i>Multi-Level Optimized Negative-Autoregulated Cas13d and crRNA Hybrid</i> (MONARCH) gene circuits that achieve a high dynamic range with low basal on-target RNA reduction while minimizing collateral activity in human kidney cells and green monkey cells most frequently used in human virology. MONARCH should bring RNA-guided RNA cutting systems to the forefront, as easily applicable, programmable tools for transcriptome engineering in biotechnological and medical applications.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acssynbio.4c00271","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142450374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Energy Aware Technology Mapping of Genetic Logic Circuits","authors":"Erik Kubaczka,&nbsp;Maximilian Gehri,&nbsp;Jérémie J. M. Marlhens,&nbsp;Tobias Schwarz,&nbsp;Maik Molderings,&nbsp;Nicolai Engelmann,&nbsp;Hernan G. Garcia,&nbsp;Christian Hochberger and Heinz Koeppl*,&nbsp;","doi":"10.1021/acssynbio.4c0039510.1021/acssynbio.4c00395","DOIUrl":"https://doi.org/10.1021/acssynbio.4c00395https://doi.org/10.1021/acssynbio.4c00395","url":null,"abstract":"<p >Energy and its dissipation are fundamental to all living systems, including cells. Insufficient abundance of energy carriers─as caused by the additional burden of artificial genetic circuits─shifts a cell’s priority to survival, also impairing the functionality of the genetic circuit. Moreover, recent works have shown the importance of energy expenditure in information transmission. Despite living organisms being non-equilibrium systems, non-equilibrium models capable of accounting for energy dissipation and non-equilibrium response curves are not yet employed in genetic design automation (GDA) software. To this end, we introduce Energy Aware Technology Mapping, the automated design of genetic logic circuits with respect to energy efficiency and functionality. The basis for this is an energy aware non-equilibrium steady state model of gene expression, capturing characteristics like energy dissipation─which we link to the entropy production rate─and transcriptional bursting, relevant to eukaryotes as well as prokaryotes. Our evaluation shows that a genetic logic circuit’s functional performance and energy efficiency are disjoint optimization goals. For our benchmark, energy efficiency improves by 37.2% on average when comparing to functionally optimized variants. We discover a linear increase in energy expenditure and overall protein expression with the circuit size, where Energy Aware Technology Mapping allows for designing genetic logic circuits with the energetic costs of circuits that are one to two gates smaller. Structural variants improve this further, while results show the Pareto dominance among structures of a single Boolean function. By incorporating energy demand into the design, Energy Aware Technology Mapping enables energy efficiency by design. This extends current GDA tools and complements approaches coping with burden <i>in vivo</i>.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acssynbio.4c00395","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142450377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing and Engineering Rhamnose-Inducible Regulatory Systems for Dynamic Control of Metabolic Pathways in <i>Streptomyces</i>.","authors":"Qian Yang, Mengao Luan, Meiyan Wang, Yuxin Zhang, Guoqiang Liu, Guoqing Niu","doi":"10.1021/acssynbio.4c00626","DOIUrl":"https://doi.org/10.1021/acssynbio.4c00626","url":null,"abstract":"<p><p>Fine-tuning gene expression is of great interest for synthetic biotechnological applications. This is particularly true for the genus <i>Streptomyces</i>, which is well-known as a prolific producer of diverse natural products. Currently, there is an increasing demand to develop effective gene induction systems. In this study, bioinformatic analysis revealed a putative rhamnose catabolic pathway in multiple <i>Streptomyces</i> species, and the removal of the pathway in the model organism <i>Streptomyces coelicolor</i> impaired its growth on minimal media with rhamnose as the sole carbon source. To unravel the regulatory mechanism of RhaR, a LacI family transcriptional regulator of the catabolic pathway, electrophoretic mobility shift assays (EMSAs) were performed to identify potential target promoters. Multiple sequence alignments retrieved a consensus sequence of the RhaR operator (<i>rhaO</i>). A synthetic biology-based strategy was then deployed to build rhamnose-inducible regulatory systems, referred to as <i>rhaRS1</i> and <i>rhaRS2</i>, by assembling the repressor/operator pair RhaR/<i>rhaO</i> with the well-defined constitutive <i>kasO*</i> promoter. Both <i>rhaRS1</i> and <i>rhaRS2</i> exhibited a high level of induced reporter activity, with no leaky expression. <i>rhaRS2</i> has been proven successful for the programmable production of actinorhodin and violacein in <i>Streptomyces</i>. Our study expanded the toolkit of inducible regulatory systems that will be broadly applicable to many other <i>Streptomyces</i> species.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Energy Aware Technology Mapping of Genetic Logic Circuits.","authors":"Erik Kubaczka, Maximilian Gehri, Jérémie J M Marlhens, Tobias Schwarz, Maik Molderings, Nicolai Engelmann, Hernan G Garcia, Christian Hochberger, Heinz Koeppl","doi":"10.1021/acssynbio.4c00395","DOIUrl":"https://doi.org/10.1021/acssynbio.4c00395","url":null,"abstract":"<p><p>Energy and its dissipation are fundamental to all living systems, including cells. Insufficient abundance of energy carriers─as caused by the additional burden of artificial genetic circuits─shifts a cell's priority to survival, also impairing the functionality of the genetic circuit. Moreover, recent works have shown the importance of energy expenditure in information transmission. Despite living organisms being non-equilibrium systems, non-equilibrium models capable of accounting for energy dissipation and non-equilibrium response curves are not yet employed in genetic design automation (GDA) software. To this end, we introduce Energy Aware Technology Mapping, the automated design of genetic logic circuits with respect to energy efficiency and functionality. The basis for this is an energy aware non-equilibrium steady state model of gene expression, capturing characteristics like energy dissipation─which we link to the entropy production rate─and transcriptional bursting, relevant to eukaryotes as well as prokaryotes. Our evaluation shows that a genetic logic circuit's functional performance and energy efficiency are disjoint optimization goals. For our benchmark, energy efficiency improves by 37.2% on average when comparing to functionally optimized variants. We discover a linear increase in energy expenditure and overall protein expression with the circuit size, where Energy Aware Technology Mapping allows for designing genetic logic circuits with the energetic costs of circuits that are one to two gates smaller. Structural variants improve this further, while results show the Pareto dominance among structures of a single Boolean function. By incorporating energy demand into the design, Energy Aware Technology Mapping enables energy efficiency by design. This extends current GDA tools and complements approaches coping with burden <i>in vivo</i>.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR-GEM: A Novel Machine Learning Model for CRISPR Genetic Target Discovery and Evaluation.","authors":"Joshua P Graham, Yu Zhang, Lifang He, Tomas Gonzalez-Fernandez","doi":"10.1021/acssynbio.4c00473","DOIUrl":"https://doi.org/10.1021/acssynbio.4c00473","url":null,"abstract":"<p><p>CRISPR gene editing strategies are shaping cell therapies through precise and tunable control over gene expression. However, limitations in safely delivering high quantities of CRISPR machinery demand careful target gene selection to achieve reliable therapeutic effects. Informed target gene selection requires a thorough understanding of the involvement of target genes in gene regulatory networks (GRNs) and thus their impact on cell phenotype. Effective decoding of these complex networks has been achieved using machine learning models, but current techniques are limited to single cell types and focus mainly on transcription factors, limiting their applicability to CRISPR strategies. To address this, we present CRISPR-GEM, a multilayer perceptron (MLP) based synthetic GRN constructed to accurately predict the downstream effects of CRISPR gene editing. First, input and output nodes are identified as differentially expressed genes between defined experimental and target cell/tissue types, respectively. Then, MLP training learns regulatory relationships in a black-box approach allowing accurate prediction of output gene expression using only input gene expression. Finally, CRISPR-mimetic perturbations are made to each input gene individually, and the resulting model predictions are compared to those for the target group to score and assess each input gene as a CRISPR candidate. The top scoring genes provided by CRISPR-GEM therefore best modulate experimental group GRNs to motivate transcriptomic shifts toward a target group phenotype. This machine learning model is the first of its kind for predicting optimal CRISPR target genes and serves as a powerful tool for enhanced CRISPR strategies across a range of cell therapies.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}