Abstract:
:One limitation of gene-directed enzyme prodrug therapy (GDEPT) is the difficulty in selectively and efficiently transducing cancer cells with the gene encoding a prodrug-converting enzyme. To circumvent this issue, we sought to move the selectivity from the gene delivery level to the protein level. We developed fusion proteins of the prodrug-activating enzyme yeast cytosine deaminase (yCD) and the oxygen-dependent degradation domain (ODDD) of HIF-1α, a domain that regulates the accumulation of HIF-1α in an oxygen-dependent manner. We called these HOPE fusions for HIF1-α Oxygen-dependent degradation domain/Prodrug-converting Enzyme. The HOPE fusions were designed to selectively accumulate in cells experiencing hypoxia and thus selectively cause conversion of the prodrug 5-fluorocytosine (5-FC) to the chemotherapeutic 5-fluorouracil (5-FU) where oxygen levels are low (e.g., at the center of a tumor). Consistent with our hypothesis, HT1080 fibrosarcoma cells transduced with HOPE fusion genes exhibited increased fusion protein accumulation and increased sensitization to 5-FC in mock-hypoxia.
journal_name
ACS Synth Bioljournal_title
ACS synthetic biologyauthors
Warren TD,Patel K,Eshleman JR,Ostermeier Mdoi
10.1021/acssynbio.9b00036subject
Has Abstractpub_date
2019-05-17 00:00:00pages
948-954issue
5issn
2161-5063journal_volume
8pub_type
杂志文章abstract::Whole cell biosensors are genetic systems that link the presence of a chemical, or other stimulus, to a user-defined gene expression output for applications in sensing and control. However, the gene expression level of biosensor regulatory components required for optimal performance is nonintuitive, and classical iter...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.9b00448
更新日期:2020-03-20 00:00:00
abstract::Allosteric proteins, which can sense different signals, are interesting biological parts for synthetic biology. In particular, the design of an artificial allosteric enzyme to sense an unnatural signal is both challenging and highly desired, for example, for a precise and dynamical control of fluxes of growth-essentia...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/sb400133g
更新日期:2015-02-20 00:00:00
abstract::The design of synthetic cells requires a detailed understanding of the relevance of genes and gene networks underlying complex cellular phenotypes. Transposon-sequencing (Tn-seq) and constraint-based metabolic modeling can be used to probe the core genetic and metabolic networks underlying a biological process. Integr...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.8b00432
更新日期:2019-01-18 00:00:00
abstract::Author: Recently, increasing research in siderophores has been dedicated to their possible medical applications in diagnostics and therapeutics for human pathogenic infections. Fusarinine C (FsC) is a natural hydroxamate siderophore that harbors three amino groups, which allow the easy chemical modification of FsC for...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.9b00026
更新日期:2019-08-16 00:00:00
abstract::Bacterial biofilms are three-dimensional networks of cells entangled in a self-generated extracellular polymeric matrix composed of proteins, lipids, polysaccharides, and nucleic acids. Biofilms can establish themselves on virtually any accessible surface and lead to varying impacts ranging from infectious diseases to...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.9b00192
更新日期:2019-07-19 00:00:00
abstract::Genetic switches in which the activity of T7 RNA polymerase (RNAP) is directly regulated by external signals are obtained with an engineering strategy of splitting the protein into fragments and using regulatory domains to modulate their reconstitutions. Robust switchable systems with excellent dark-off/light-on prope...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.6b00248
更新日期:2017-02-17 00:00:00
abstract::A negating functionality is fundamental to information processing of logic circuits within cells and computers. Aiming to adapt unutilized electronic concepts to the interrogation of signaling circuits in cells, we first took a bottom-up strategy whereby we created protein-based devices that perform negating Boolean l...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/sb500222z
更新日期:2014-09-19 00:00:00
abstract::Feedback allows biological systems to control gene expression precisely and reliably, even in the presence of uncertainty, by sensing and processing environmental changes. Taking inspiration from natural architectures, synthetic biologists have engineered feedback loops to tune the dynamics and improve the robustness ...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.8b00040
更新日期:2018-05-18 00:00:00
abstract::Cell-free protein synthesis (CFPS) is a widely used research tool in systems and synthetic biology. However, if CFPS is to become a mainstream technology for applications such as point of care manufacturing, we must understand the performance limits and costs of these systems. Toward this question, we used sequence sp...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.7b00465
更新日期:2018-08-17 00:00:00
abstract::A significant bottleneck in synthetic biology involves screening large genetically encoded libraries for desirable phenotypes such as chemical production. However, transcription factor-based biosensors can be leveraged to screen thousands of genetic designs for optimal chemical production in engineered microbes. In th...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.9b00255
更新日期:2019-10-18 00:00:00
abstract::We present the OpenPlant toolkit, a set of interlinked resources and techniques to develop Marchantia as testbed for bioengineering in plants. Marchantia is a liverwort, a simple plant with an open form of development that allows direct visualization of gene expression and dynamics of cellular growth in living tissues...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.9b00511
更新日期:2020-04-17 00:00:00
abstract::The Design-Build-Test-Learn (DBTL) cycle, facilitated by exponentially improving capabilities in synthetic biology, is an increasingly adopted metabolic engineering framework that represents a more systematic and efficient approach to strain development than historical efforts in biofuels and biobased products. Here, ...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.9b00020
更新日期:2019-06-21 00:00:00
abstract::Materials synthesized by organisms, such as bones and wood, combine the ability to self-repair with remarkable mechanical properties. This multifunctionality arises from the presence of living cells within the material and hierarchical assembly of different components across nanometer to micron scales. While creating ...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.8b00448
更新日期:2019-01-18 00:00:00
abstract::Engineered genetic systems are commonly unstable; if propagated, they evolve to reverse or modify engineered elements because the elements impair fitness. A goal of synthetic biology is thus to anticipate and avoid detrimental engineering, but little is yet known about which types of elements cause problems in differe...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/sb300040v
更新日期:2012-09-21 00:00:00
abstract::Quantification of biology's central dogma (transcription and translation) is pursued by a variety of methods. Direct, immediate, and ongoing quantification of these events is difficult to achieve. Common practice is to use fluorescent or luminescent proteins to report indirectly on prior cellular events, such as turni...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.8b00450
更新日期:2019-05-17 00:00:00
abstract::Microbial mutualisms play critical roles in a diverse number of ecosystems and have the potential to improve the efficiency of bioproduction for desirable chemicals. We investigate the growth of a photosynthetic cyanobacterium, Synechococcus elongatus PCC 7942, and a diazotroph, Azotobacter vinelandii, in coculture. F...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.6b00107
更新日期:2016-09-16 00:00:00
abstract::Simple computation can be performed using the interactions between single-stranded molecules of DNA. These interactions are typically toehold-mediated strand displacement reactions in a well-mixed solution. We demonstrate that a DNA circuit with tethered reactants is a distributed system and show how it can be describ...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.5b00275
更新日期:2016-08-19 00:00:00
abstract::Phenazine-1-carboxamide (PCN) produced by multifarious Pseudomonas strains represents a promising candidate as a new metabolite pesticide due to its broad-spectrum antifungal activity and capacity to induce systemic resistance in plants. The rice rhizosphere Pseudomonas strain PA1201 contains two reiterated gene clust...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.0c00161
更新日期:2020-07-17 00:00:00
abstract::Medium-chain fatty acids (MCFAs) are key intermediates in the synthesis of medium-chain chemicals including α-olefins and dicarboxylic acids. In bacteria, microbial production of MCFAs is limited by the activity and product profile of fatty acyl-ACP thioesterases. Here, we engineer a heterologous bacterial medium-chai...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.7b00334
更新日期:2018-05-18 00:00:00
abstract::The microbial ability to resist stressful environmental conditions and chemical inhibitors is of great industrial and medical interest. Much of the data related to mutation-based stress resistance, however, is scattered through the academic literature, making it difficult to apply systematic analyses to this wealth of...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.6b00150
更新日期:2016-12-16 00:00:00
abstract::A streamlined approach toward the rapid fabrication of streptavidin-biotin-based protein microarrays was investigated. First, using our engineered versatile plasmid (pBADcM-tBirA) and an optimal coexpression strategy for biotin ligase and biotin acceptor peptide (BAP) chimeric recombinant protein, an autogeneration sy...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.0c00343
更新日期:2020-09-18 00:00:00
abstract::The cell contents are encapsulated within a compartment, the volume of which is a fundamental physical parameter that may affect intracompartmental reactions. However, there have been few studies to elucidate whether and how volume changes alone can affect the reaction kinetics. It is difficult to address these questi...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/sb300041z
更新日期:2012-09-21 00:00:00
abstract::While engineered chimeric antigen receptor (CAR) T cells have shown promise in detecting and eradicating cancer cells within patients, it remains difficult to identify a set of truly cancer-specific CAR-targeting cell surface antigens to prevent potentially fatal on-target off-tumor toxicity against other healthy tiss...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.9b00175
更新日期:2019-10-18 00:00:00
abstract::Gene expression noise arises from stochastic variation in the synthesis and degradation of mRNA and protein molecules and creates differences in protein numbers across populations of genetically identical cells. Such variability can lead to imprecision and reduced performance of both native and synthetic networks. In ...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.8b00279
更新日期:2018-11-16 00:00:00
abstract::Novel approaches are needed to combat antibiotic resistance. Here, we describe a computational-experimental framework for the discovery of novel cryptic antimicrobial peptides (AMPs). The computational platform, based on previously validated antimicrobial scoring functions, indicated the activation peptide of pepsin A...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.8b00084
更新日期:2018-09-21 00:00:00
abstract::We have previously engineered green/red and red/far red photoreversible E. coli phytochrome and cyanobacteriochrome (CBCR) two-component systems (TCSs) and utilized them to program tailor-made gene expression signals for gene circuit characterization. Here, we transport the UV-violet/green photoreversible CBCR TCS Uir...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.6b00068
更新日期:2016-07-15 00:00:00
abstract::Understanding the molecular mechanisms underlying antibiotic resistance requires concerted efforts in enzymology and medicinal chemistry. Here we describe a new synthetic biology approach to antibiotic development, where the presence of tetracycline antibiotics is linked to a life-death selection in Saccharomyces cere...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.8b00121
更新日期:2018-08-17 00:00:00
abstract::A defining goal of synthetic biology is to develop biomaterials with superior performance and versatility. Here we introduce a purely genetically encoded and self-assembling biopolymer based on the SpyTag-SpyCatcher chemistry. We show the application of this polymer for highly efficient uranyl binding and extraction f...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.8b00223
更新日期:2018-10-19 00:00:00
abstract::Synthetic biology is today harnessing the design of novel and greener biosynthesis routes for the production of added-value chemicals and natural products. The design of novel pathways often requires a detailed selection of enzyme sequences to import into the chassis at each of the reaction steps. To address such desi...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/acssynbio.5b00294
更新日期:2016-06-17 00:00:00
abstract::In response to emergent antibiotic resistance, new strategies are needed to enhance the effectiveness of existing antibiotics. Here, we describe a phagemid-delivered, RNA-mediated system capable of directly knocking down antibiotic resistance phenotypes. Small regulatory RNAs (sRNAs) were designed to specifically inhi...
journal_title:ACS synthetic biology
pub_type: 杂志文章
doi:10.1021/sb500033d
更新日期:2014-12-19 00:00:00