Regulation of oligonucleotide adsorption by a thermo and pH dual-responsive copolymer layer

2021 ◽  
Author(s):  
Chao Feng ◽  
Jiang-xue Mu ◽  
Chunlai Ren
Keyword(s):  
Gene Expression ◽  
Treatment Efficacy ◽  
Therapeutic Agents ◽  
Great Promise ◽  
Targeting Efficiency ◽  
Dual Responsive ◽  
Inhibit Gene Expression

Oligonucleotides hold great promise as therapeutic agents to specifically and selectively inhibit gene expression. In order to achieve better targeting efficiency and treatment efficacy, nanocarriers that are dual-responsive to both...

Antithrombotic Therapy for DVT/PE

1997 ◽  
Vol 17 (03) ◽  
pp. 161-162
Author(s):  
Thomas Hyers
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Oral Anticoagulants ◽  
Cost Effective ◽  
Therapeutic Agents ◽  
Great Promise ◽  
Term Therapy ◽  
Low Molecular Weight ◽  
Long Term Therapy

SummaryProblems with unfractionated heparin as an antithrombotic have led to the development of new therapeutic agents. Of these, low molecular weight heparin shows great promise and has led to out-patient therapy of DVT/PE in selected patients. Oral anticoagulants remain the choice for long-term therapy. More cost-effective ways to give oral anticoagulants are needed.

scholarly journals Candidate therapeutic agents for hepatocellular cancer can be identified from phenotype-associated gene expression signatures

Cancer ◽  
2009 ◽  
Vol 115 (16) ◽  
pp. 3738-3748 ◽  
Author(s):  
Chiara Braconi ◽  
Fanyin Meng ◽  
Erica Swenson ◽  
Lyudmyla Khrapenko ◽  
Nianyuan Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Cancer ◽  
Therapeutic Agents ◽  
Gene Expression Signatures

scholarly journals VipariNama: RNA viral vectors to rapidly elucidate the relationship between gene expression and phenotype

2021 ◽  
Author(s):  
Arjun Khakhar ◽  
Cecily Wang ◽  
Ryan Swanson ◽  
Sydney Stokke ◽  
Furva Rizvi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Viral Vectors ◽  
Viral Vector ◽  
Tobacco Rattle Virus ◽  
Plant Size ◽  
Great Promise ◽  
Attractive Alternative ◽  
Gibberellin Biosynthesis ◽  
In Planta

Abstract Synthetic transcription factors have great promise as tools to help elucidate relationships between gene expression and phenotype by allowing tunable alterations of gene expression without genomic alterations of the loci being studied. However, the years-long timescales, high cost, and technical skill associated with plant transformation have limited their use. In this work we developed a technology called VipariNama (ViN) in which vectors based on the Tobacco Rattle Virus (TRV) are used to rapidly deploy Cas9-based synthetic transcription factors and reprogram gene expression in planta. We demonstrate that ViN vectors can implement activation or repression of multiple genes systemically and persistently over several weeks in Nicotiana benthamiana, Arabidopsis (Arabidopsis thaliana), and tomato (Solanum lycopersicum). By exploring strategies including RNA scaffolding, viral vector ensembles, and viral engineering, we describe how the flexibility and efficacy of regulation can be improved. We also show how this transcriptional reprogramming can create predictable changes to metabolic phenotypes, such as gibberellin biosynthesis in N. benthamiana and anthocyanin accumulation in Arabidopsis, as well as developmental phenotypes, such as plant size in N. benthamiana, Arabidopsis, and tomato. These results demonstrate how ViN vector-based reprogramming of different aspects of gibberellin signaling can be used to engineer plant size in a range of plant species in a matter of weeks. In summary, VipariNama accelerates the timeline for generating phenotypes from over a year to just a few weeks, providing an attractive alternative to transgenesis for synthetic transcription factor-enabled hypothesis testing and crop engineering.

scholarly journals Cytosine and adenine deaminase base-editors induce broad and nonspecific changes in gene expression and splicing

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jiao Fan ◽  
Yige Ding ◽  
Chao Ren ◽  
Ziguo Song ◽  
Jie Yuan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Double Strand Breaks ◽  
Great Promise ◽  
Single Nucleotide ◽  
Strand Breaks ◽  
Dna Base ◽  
Target Dna ◽  
Single Nucleotide Variations ◽  
Adenine Deaminase ◽  
Target Rna

AbstractCytosine or adenine base editors (CBEs or ABEs) hold great promise in therapeutic applications because they enable the precise conversion of targeted base changes without generating of double-strand breaks. However, both CBEs and ABEs induce substantial off-target DNA editing, and extensive off-target RNA single nucleotide variations in transfected cells. Therefore, the potential effects of deaminases induced by DNA base editors are of great importance for their clinical applicability. Here, the transcriptome-wide deaminase effects on gene expression and splicing is examined. Differentially expressed genes (DEGs) and differential alternative splicing (DAS) events, induced by base editors, are identified. Both CBEs and ABEs generated thousands of DEGs and hundreds of DAS events. For engineered CBEs or ABEs, base editor-induced variants had little effect on the elimination of DEGs and DAS events. Interestingly, more DEGs and DAS events are observed as a result of over expressions of cytosine and adenine deaminases. This study reveals a previously overlooked aspect of deaminase effects in transcriptome-wide gene expression and splicing, and underscores the need to fully characterize such effects of deaminase enzymes in base editor platforms.

scholarly journals VipariNama: RNA vectors to rapidly reprogram plant morphology and metabolism

2020 ◽  
Author(s):  
Arjun Khakhar ◽  
Cecily Wang ◽  
Ryan Swanson ◽  
Sydney Stokke ◽  
Furva Rizvi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Plant Morphology ◽  
Plant Size ◽  
Great Promise ◽  
Attractive Alternative ◽  
Biological Processes ◽  
In Planta ◽  
Transcriptional Reprogramming ◽  
Long Timescales

AbstractSynthetic transcription factors have great promise as tools to explore biological processes. By allowing precise alterations in gene expression, they can help elucidate relationships between gene expression and plant morphology or metabolism. However, the years-long timescales, high cost, and technical skill associated with plant transformation have dramatically slowed their use. In this work, we developed a new platform technology called VipariNama (ViN) in which RNA vectors are used to rapidly deploy synthetic transcription factors and reprogram gene expression in planta. We demonstrate how ViN vectors can direct activation or repression of multiple genes, systemically and persistently over several weeks, and in multiple plant species. We also show how this transcriptional reprogramming can create predictable changes to metabolic and morphological phenotypes in the model plants Nicotiana benthamiana and Arabidopsis thaliana in a matter of weeks. Finally, we show how a model of gibberellin signaling can guide ViN vector-based reprogramming to rapidly engineer plant size in both model species as well as the crop Solanum lycopersicum (tomato). In summary, using VipariNama accelerates the timeline for generating phenotypes from over a year to just a few weeks, providing an attractive alternative to transgenesis for synthetic transcription factor-enabled hypothesis testing and crop engineering.

scholarly journals How the Avidity of Polymerase Binding to the -35/-10 Promoter Sites Affects Gene Expression

2019 ◽  
Author(s):  
Tal Einav ◽  
Rob Phillips
Keyword(s):  
Gene Expression ◽  
Rna Polymerase ◽  
Regulatory Elements ◽  
Physical Principle ◽  
Regulatory Sequences ◽  
Energy Matrix ◽  
Cellular Behavior ◽  
Inhibit Gene Expression ◽  
Small Set ◽  
Polymerase Binding

AbstractAlthough the key promoter elements necessary to drive transcription inEscherichia colihave long been understood, we still cannot predict the behavior of arbitrary novel promoters, hampering our ability to characterize the myriad of sequenced regulatory architectures as well as to design novel synthetic circuits. This work builds on a beautiful recent experiment by Urtechoet al.who measured the gene expression of over 10,000 promoters spanning all possible combinations of a small set of regulatory elements. Using this data, we demonstrate that a central claim in energy matrix models of gene expression – that each promoter element contributes independently and additively to gene expression – contradicts experimental measurements. We propose that a key missing ingredient from such models is the avidity between the -35 and -10 RNA polymerase binding sites and develop what we call arefined energy matrixmodel that incorporates this effect. We show that this the refined energy matrix model can characterize the full suite of gene expression data and explore several applications of this framework, namely, how multivalent binding at the -35 and -10 sites can buffer RNAP kinetics against mutations and how promoters that bind overly tightly to RNA polymerase can inhibit gene expression. The success of our approach suggests that avidity represents a key physical principle governing the interaction of RNA polymerase to its promoter.Significance StatementCellular behavior is ultimately governed by the genetic program encoded in its DNA and through the arsenal of molecular machines that actively transcribe its genes, yet we lack the ability to predict how an arbitrary DNA sequence will perform. To that end, we analyze the performance of over 10,000 regulatory sequences and develop a model that can predict the behavior of any sequence based on its composition. By considering promoters that only vary by one or two elements, we can characterize how different components interact, providing fundamental insights into the mechanisms of transcription.

The Circadian Clock inArabidopsisRoots Is a Simplified Slave Version of the Clock in Shoots

Science ◽  
2008 ◽  
Vol 322 (5909) ◽  
pp. 1832-1835 ◽  
Author(s):  
Allan B. James ◽  
José A. Monreal ◽  
Gillian A. Nimmo ◽  
Ciarán L. Kelly ◽  
Pawel Herzyk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Circadian Clock ◽  
Clock Genes ◽  
Plant Cells ◽  
Feedback Loops ◽  
Circadian Oscillator ◽  
Inhibit Gene Expression ◽  
Organ Specific ◽  
Plant Clock

The circadian oscillator in eukaryotes consists of several interlocking feedback loops through which the expression of clock genes is controlled. It is generally assumed that all plant cells contain essentially identical and cell-autonomous multiloop clocks. Here, we show that the circadian clock in the roots of matureArabidopsisplants differs markedly from that in the shoots and that the root clock is synchronized by a photosynthesis-related signal from the shoot. Two of the feedback loops of the plant circadian clock are disengaged in roots, because two key clock components, the transcription factors CCA1 and LHY, are able to inhibit gene expression in shoots but not in roots. Thus, the plant clock is organ-specific but not organ-autonomous.

scholarly journals Gene Expression Signatures Associated With Survival Times of Pediatric Patients With Biliary Atresia Identify Potential Therapeutic Agents

2019 ◽  
Vol 157 (4) ◽  
pp. 1138-1152.e14 ◽  
Author(s):  
Zhenhua Luo ◽  
Pranavkumar Shivakumar ◽  
Reena Mourya ◽  
Sridevi Gutta ◽  
Jorge A. Bezerra
Keyword(s):  
Gene Expression ◽  
Biliary Atresia ◽  
Pediatric Patients ◽  
Therapeutic Agents ◽  
Survival Times ◽  
Gene Expression Signatures
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