Arrakis Therapeutics, a pioneering biopharmaceutical company announced that it has released SHAPEware™ as open-source software for the research community with the goal of promoting and facilitating the use of SHAPE-based approaches to study RNA structure. SHAPEware is a computational tool for researchers to explore and predict the secondary structure and potential ligand binding sites in an RNA.
SHAPE (Selective 2′ Hydroxyl Acylation analyzed by Primer Extension), the most widely used approach for probing RNA secondary structure, was developed by Kevin Weeks, Ph.D., and colleagues at the University of North Carolina in 2005.1 SHAPE studies provide scientists with experimental assessment of predicted loops, bulges and pockets in the two-dimensional structures of RNA. The resulting integrated structural prediction enables biological insight into RNA function and detection of ligand binding sites within the RNA.
SHAPEware offers a standardized and modular set of tools for scientists to analyze data generated by SHAPE methodologies and was initially developed by Arrakis to streamline and standardize its own analysis of the SHAPE data that the company is generating in its proprietary drug discovery efforts to design RNA-targeted small molecules (rSMs).
“We are thrilled to share SHAPEware with the broader community of RNA experts,” said Russ Petter, PhD, Founder and Chief Scientific Officer at Arrakis. “The field of RNA structure is advancing rapidly and open-source software allows us to accelerate the best thinking from hundreds of potential users.”
SHAPEware will help researchers identify and evaluate the distinct characteristics of folded RNA through the following features and upgrades:
SHAPEware is designed to be highly modular and customizable, allowing users to evaluate and compare results from different analytic algorithms and SHAPE methodologies.
The initial launch of SHAPEware includes a module to analyze data from SHAPE-MaP (mutational profiling) experiments.
Arrakis continues to develop and adapt novel SHAPE methodologies to study RNA structure. It is anticipated that additional updates and modules will be added.
The SHAPEware open-source software can be downloaded at www.shapewareRNA.com, and the free license requires users to share feedback and any modifications or improvements with the community.
SHAPE is an acronym for selective 2′-hydroxyl acylation analyzed by primer extension, developed by Kevin Weeks, Ph.D., and colleagues at the University of North Carolina in 2005, and describes the chemical reaction that is used to assess the flexibility of RNA at each nucleotide in any given sequence. This information can be used to establish the secondary structure of an RNA, to monitor structural differences between related RNAs or a single RNA in different states, and to infer ligand binding sites. Several SHAPE-based methodologies have been developed in academic laboratories: SHAPE-Seq, SHAPE-MaP (SHAPE followed by mutational profiling) and icSHAPE (in vivo click selective SHAPE), each requiring different experimental protocols and analysis software.
About RNA-targeted Small Molecules (rSMs)
Emerging insights and technologies focused on understanding the structure of RNA enable the design of RNA-targeted small molecules, or rSMs, a new class of medicines that directly bind and modify the biological function of RNA to treat disease. Unlike conventional drug discovery approaches that focus on proteins, an rSM is designed to modulate function of an individual RNA, and, in the case of mRNA, the expressed protein, by selectively binding to specific, predictable structures in functional regions in the RNA. This new drug discovery approach enables the design of small-molecule drugs that can unlock the therapeutic potential of well-known targets that are not accessible with today’s drugs, as well as identifying new drug targets to intervene in diseases in new ways.
About Arrakis Therapeutics
Arrakis Therapeutics is a biopharmaceutical company pioneering the discovery of a new class of medicines that directly target RNA. The company has developed a proprietary platform to identify new RNA targets and drug candidates to treat diseases not addressed by today’s medicines. Arrakis is building a proprietary pipeline of RNA-targeted small molecules (rSMs) focused on neurologic diseases, cancer, and rare genetic diseases.
Arrakis was founded in 2015 by Russell C. Petter, Ph.D., Alan Walts, Ph.D., Henri Termeer and Raj Parekh, Ph.D. with a vision to create a proprietary, transformational discovery platform that identifies small-molecule drugs that act directly on disease-causing RNA. The company was established with seed funding provided by Advent Life Sciences and Henri Termeer. The company brings together scientific leaders in RNA structure, chemistry and biology, along with a highly experienced management team and the backing of leading life sciences investors. The company is located in Waltham, Mass. Please visit www.arrakistx.com
For Arrakis Therapeutics
Kathryn Morris, 914-204-6412