Author: joseph@dnasoftware.com
DNA Software, Inc., awarded an NIH SBIR fast track grant
NIH SBIR fast track grant
DNA Software, Inc., awarded an NIH SBIR fast track grant for the development of “An Antisense Design and Simulation Platform”
In this grant proposal “An Automated Antisense Design and Simulation Platform”, a comprehensive molecular diagnostics software tool that is specific to the design and simulation of antisense oligonucleotide analog probes will be developed. The application of antisense technologies to the study of human diseases has been proven in the literature for cancer, immune deficiency disorders, diabetes, muscular dystrophy and cardiovascular disease, hepatitis A and C, HIV, SARS-coronovirus, Ebola, Dengue Fever, paramyxoviruses (measles), and the West Nile virus. However, the progress of directed antisense research has been slow due to the absence of antisense oligonucleotide analog thermodynamic and kinetic databases, and because the currently used rule-of-thumb design strategies rarely ever initially produce effective probes. Many researchers are then forced to design a small library of probes against the same genomic target to increase their likelihood of success, which is very costly in both time and financing. The proposed Antisense Design and Simulation Platform will enable the researchers of human diseases by providing a tool for the directed research and evaluation of human and viral genomic targets so that rationally designed antisense oligonucleotide analogs may be used as a molecular diagnostics tool.
Developmental Strategies
The developmental strategies for producing the proposed platform are to update existing thermodynamic and kinetic databases and to deploy them on the Antisense Design and Simulation Platform, as outlined in the following specific aims: Aim 1.1: Perform 16 thermodynamic melts each for the fluorophore, biotin and quencher labeled PNA and morpholino antisense probes, and for the phosphorothioate/LNA antisense gap-mer probes to demonstrate the feasibility of applying the nearest-neighbor thermodynamic model to these systems. Aim 1.2: Add the thermodynamic parameters determined in Aim 1.1 to the existing PCR platform Visual OMP to demonstrate the feasibility of applying design and simulation algorithms to modified antisense oligonucleotide analogs. Aim 2.1: Complete the thermodynamic library for the fluorophore, and quencher labeled PNA and morpholino antisense probes, and for the phosphorothioate/LNA antisense gap-mer probes. Aim 2.2: Perform kinetics experiments on modified morpholino/RNA and PNA/RNA duplexes, and develop predictive mathematical models for the rates of Morpholino/RNA and PNA/RNA hybridization and unfolding. Aim 2.3: Engineer a fully automated Antisense Design and Simulation Platform that will allow researchers to design specific and sensitive antisense probes with minimal user inputs. By the end of this project a fully automated Antisense Design and Simulation Platform will have been designed, tested, and debugged, and made available to antisense researchers for the purpose of beta-testing the commercial product.
Impact
PUBLIC HEALTH RELEVANCE: This project will directly impact public health by providing a comprehensive software tool for the design and simulation of antisense oligonucleotide analog probes, where no other comprehensive antisense software tools exist. The efficacy of applying antisense technologies to human diseases has been proven, using a trial-and-error approach to a number of human diseases, such as: cancer, immune deficiency disorders, diabetes, muscular dystrophy and cardiovascular disease, hepatitis A and C, HIV, SARS-coronovirus, Ebola, Dengue Fever, paramyxoviruses (measles), and the West Nile virus. The proposed Antisense Design and Simulation Platform will benefit the researchers of human diseases by providing an optimized molecular diagnostic tool for the directed research and rational evaluation of human and viral genomic targets.
Dr. John SantaLucia honored with Award
Distinguished Entrepreneur
Dr. John SantaLucia honored with “Distinguished Entrepreneur” Award by Wayne State University.
On March 10, 2011 John SantaLucia was presented the “WSU Distinguished Entrepreneur” award from Wayne State University President, Allan D. Gilmour and Vice President of Research, Hillary H. Ratner. The award was presented based upon Professor SantaLucia’s scientific and entrepreneurial success with DNA Software, Inc.
ThermoBLAST and VisualOMP in H1N1 Design
H1N1 Design
ThermBLAST and Visual OMP Application in H1N1 Design Published in Journal of Clinical Microbiology…Read More
DNA Software Publishes RNA-DNA Parameters
RNA-DNA Parameters
DNA Software Publishes RNA-DNA Parameters in Nucleic Acid Research…Read More
DNA Software, Inc., awarded an NIH grant
NIH grant
DNA Software, Inc., awarded an NIH SBIR fast track grant for the development of “Software for the Accurate de novo 3D Structure Prediction of RNA”
RNA-123TM Structural Biology Software
Introduction:
The discovery of new and interesting RNA sequences from genome sequencing projects, and the urgency to unravel their functions and develop new therapeutics, has led to a dramatic need for RNA three dimensional (3D) structural information. Current experimental methods for 3D structure determination of nucleic acids such as X-ray crystallography and NMR cannot keep pace with the daily discovery of sequences that need representative structures to be solved or modeled. Thus, there is a clear need for accurate 3D structure prediction tools that require only the primary sequence as input and can incorporate experimental constraint information when available. RNA-123™ has been developed specifically for this purpose with a major advantage of being automated, easy to use and also runs fast on a personal computer even when modeling large structures such as the ribosome. Additionally, the force field has been developed specifically for RNA which is a better approach than relying on protein prediction methodologies to predict RNA structure despite the significant differences between these two groups of molecules.
Overview:
DNA Software, Inc. has developed a suite of software tools called RNA-123™ (RNA Primary–Secondary-Tertiary Structure) for RNA structural analysis, RNA homology modeling, and RNA de novo prediction. RNA-123™ has a unique force field specifically optimized for RNA. This tool has demonstrated success in homology modeling of large RNA-protein complexes such as the 70S ribosomal structure of Pseudomonas aeruginosa.
Validation:
Validation studies have been carried out to assess the automated homology modeling approach. As an example, the Thermus Thermophilus 30S ribosomal subunit was modeled using the published 30S crystal structures of the E. coli ribosome (PDB ID 2AVY) as a template and vice versa. This study has resulted low-energy structural models of near crystal structure quality, (RMSDs between predicted models and published crystal structures is < 4 Å) with correctly predicted base pairing, stacking and tertiary interactions. Additionally, the robustness of the tool has been demonstrated through a validation study utilizing a diverse set of RNA targets such as riboswitches, ribozymes, and ribosomes.
Summary of Functionalities:
- RNA Homology modeling
- RNA De novo structure prediction
- Structure-based sequence alignment –(SBSA)
- RNA secondary and tertiary structure visualization GUI
- Tertiary structure editing, structure optimization and analysis
- Secondary structure folding
Availability:
RNA-123™ will be available by licensing to academic (with discounted pricing), non-profit, and industrial users. RNA-123™ is written in C++ and currently runs on Windows operating systems with implementations for LINUX and web access under development. RNA-123™ is scheduled for release in the spring of 2011.
Dr. John SantaLucia named President and CEO of DNAS
CEO of DNAS
Ann Arbor, MI – Dr. John SantaLucia, Jr. has been named President and CEO of DNA Software, Inc.
Dr. SantaLucia’s appointment follows former CEO Donald Hicks.
Dr. SantaLucia, a world-renowned expert in nucleic acid chemistry, most recently served as Chief Scientific Officer at DNAS. He helped to co-found DNA Software in 2000 to commercialize the advances in nucleic acid thermodynamics discovered throughout his illustrious career, which includes citation in more than 4000 publications. Dr. SantaLucia’s published thermodynamic parameters for nucleic acid hybridization are widely used throughout the field. As a result of Dr. SantaLucia’s expertise and influence, DNA Software’s technologies have become the standard of excellence for nucleic acid research and diagnostics development.
Dr. SantaLucia holds a B.S. in Chemistry from Clarkson University, a PhD from the University of Rochester and completed his postdoctoral work at the University of California at Berkeley.
About DNA Software, Inc.
DNA Software, Inc. provides the most accurate and comprehensive software tools for assay development and nucleic acid research. DNA Software serves such customers as the CDC, USDA, FDA, Roche, Novartis, Johnson & Johnson, Smiths Detection, and Luminex amongst many other leaders in the life sciences.
DNA Software is a unique software company considering that it conducts original wet lab research. The company’s software programs are the most accurate and comprehensive tools available because their advanced algorithms and models are driven by a large database of thousands of diverse, wet lab-derived, experimental results. DNA Software’s tools correctly design and simulate complicated experiments on the first attempt. Customers can simulate thousands of experiments with the software before running a single experiment in a wet lab. Thus, DNA Software’s technologies save customers significant time, resources, and money that would have been wasted on trial-and-error experimentation.
DNA Software offers contract research, custom software development, commercial web applications, and scientific consulting for nucleic acid research. The company also licenses packaged software tools that help scientists quickly and accurately develop new assays, diagnostics, and therapeutics. The company has recently expanded its original DNA and RNA-based, molecular biology solutions to include modified nucleotides, oligonucleotide kinetics, and structural biology.
Software for Modified Oligos, Target Accessibility, Off-Target Amplicons
Software for Modified Oligos
ANN ARBOR, MI – Feb. 4, 2010 – DNA Software, Inc. is pleased to announce the release of significant updates to its OMP™ (Oligonucleotide Modeling Platform™), ThermoBLAST™, and Modifieds™ software products. These updates now allow users to (1) conduct in silico experiments with oligos containing modified nucleotides, (2) graph of target accessibility and complexity, and (3) detect off-target amplicons and view them in a virtual gel.
DNA Software is a pioneering sciences and software company that is focused on original wet lab research, cutting-edge software development, continuous product improvement, and first-rate customer service. In addition to expert technical support, DNA Software’s customers automatically receive software updates as part of their annual product license.
In Silico Experiments with Modifieds Oligonucleotides:
Oligos with modified nucleotides are commonly used for: designing probes with high sensitivity and specificity, designing siRNAs with high efficacy, and performing assays of epigenetic gene regulation.
DNA Software, Inc.’s unique Modifieds™ module enables you to accurately:
- predict secondary structure of oligos and targets with modified nucleotides
- design and optimize hybridization-based experiments that include modified nucleotides
- scan modified oligos against large genome databases to detect false positives and off-target effects
Evaluating Target Accessibility and Complexity:
Primers and probes designed against targets with a high degree of secondary structure (i.e. low target accessibility) can result in false negatives due to low sensitivity. Conversely, primers and probes designed against targets with low complexity can result in false positives due to low specificity.
DNA Software’s target accessibility and complexity graph within Visual OMP™ indicates relative accessibility and complexity of regions within a target sequence to aid users in designing sequences against optimal target regions.
Detecting Off-Target Amplicons:
PCR primers often hybridize to sequences other than their intended targets. Extensible off-target primer hybridizations may result in the amplification of unintended products during PCR.
DNA Software’s amplicon detector within ThermoBLAST™ uses the genome scanning capability of ThermoBLAST™ to find extensible hybridizations that result in the amplification of off-target amplicons. The amplicon detector then displays all amplicons on a virtual gel, which allows users to quickly verify the specificity of PCR primers without running a gel in a wet lab.
About DNA Software, Inc.
DNA Software, Inc. was founded in 2000 to commercialize the advances in nucleic acid chemistry discovered by world-renowned expert Dr. John SantaLucia, Jr. (the company’s Chief Scientific Officer). DNA Software’s technologies have become the standard of excellence for nucleic acid research and diagnostics development.
DNA Software is a unique software company considering that it conducts original wet lab research. The company’s software programs are the most accurate and comprehensive tools available because its advanced algorithms and models are driven by a large database of thousands of diverse, wet lab-derived, experimental results. DNA Software’s tools correctly design and simulate complicated experiments on the first attempt. Customers can simulate thousands of experiments with the software before running a single experiment in a wet lab. Thus, DNA Software’s technologies save customers significant time, resources, and money that would have been wasted on trial-and-error experimentation.
DNA Software offers contract research, custom software development, commercial web applications, and scientific consulting for nucleic acid research. The company also licenses packaged software tools that help scientists quickly and accurately develop new assays, diagnostics, and therapeutics. OMP™ (Oligonucleotide Modeling Platform™), the core engine that runs all of DNA Software’s tools, models in silico the folding and hybridization of nucleic acids with exception accuracy. Visual OMP™ is a platform program for the prediction of nucleic acid secondary structure plus the design, simulation, and optimization of probes/primers, RT-PCR, qPCR, Multiplex PCR, Taqman, Beacons, Scorpions, Microarrays, SNP detection, FRET assays, RNAi, LATE-PCR, plus new formats. ThermoBLAST™ quickly and accurately scans DNA, RNA, or modified oligonucleotides against large genome databases, identifies all hybridizations under actual reaction conditions, and detects all extensible, off-target amplicons. The Modifieds™ module adds modified nucleotides (e.g. LNA, PNA, Morpholino, Deoxyuridine-DNA, 5-Methylcytosine-DNA, 2’-O-Methyl-RNA, Phosphorothioate, Inosine, Isocytosine, Isoguanine, plus many more) to OMP™ and ThermoBLAST™. OMP Developer Edition™ (OMP DE™) and ThermoBLAST Developer Edition™ (TB DE™) bring customizable, command line, high-throughput computing power to large assay design and genome scanning projects or enterprise applications.
The company has expanded its original DNA and RNA-based, molecular biology solutions to include modified nucleotides, oligonucleotide kinetics, and structural biology.