Shape Therapeutics (ShapeTX) is developing a new generation of gene therapies for some of the most daunting genetic. Its RNA technologies leverage machinery already present in human cells to correct genetic mutations, while avoiding immunogenicity and DNA damage. This process aims provide safer treatments that work with the body, not against it.
Here is how ShapeTX describes its mission: “We believe the cure is in you, we let biology reveal the way.” This concept is central to the ways synthetic biology is shaping a new path of therapies, especially in oncology.
ShapeTx was founded on the work of Dr. Prashant Mali, Assistant Professor of Bioengineering at UCSD, who, during his postdoctoral fellowship in the George Church laboratory at Harvard Medical School, pioneered the use of CRISPR in human cells. ShapeTx RNAfix™ platform is built upon his lab’s most recent work demonstrating in vivo use of guide RNAs to recruit native ADARs and to fix mutations in multiple rare genetic disease mouse models.
What is tRNA?
A transfer RNA (tRNA) is a special kind of RNA molecule. Its job is to match an mRNA codon with the amino acid it codes for. You can think of it as a kind of molecular bridge between the two. Each tRNA contains a set of three nucleotides called an anticodon. The anticodon of a given tRNA can bind to one or a few specific mRNA codons. The tRNA molecule also carries an amino acid: specifically, the one encoded by the codons that the tRNA binds.
tRNAs bind to mRNAs inside of a protein-and-RNA structure called the ribosome. As tRNAs enter slots in the ribosome and bind to codons, their amino acids are linked to the growing polypeptide chain in a chemical reaction. The end result is a polypeptide whose amino acid sequence mirrors the sequence of codons in the mRNA.
The company’s ShapeTX gene therapy platform comprises RNAskip™, RNAfix™, and RNAswitch™ payload technology, next-generation tissue-specific AAVid™ delivery technology, and SquareBio, a solution to scalable gene therapy manufacturing based on industrialization of human stable cell lines.
“RNA is the software of life. We now have next-generation tools to ‘debug’ the source code of genetic diseases like Parkinson’s by targeting RNA directly in the brain. It will be quite exciting to move our RNA editing and tissue-specific AAV delivery technology to the next phase of their development,” said Francois Vigneault, PhD., President and CEO.
According to the company, mutations in DNA are carried into mutated RNA which changes how a single letter is translated into a protein. A misfire caused by a single DNA letter change can lead to dysfunctional or toxic protein products.
Many upcoming gene editing approaches, like CRISPR or base editing, rely on using foreign proteins to initiate genetic changes in the cell. However, our immune system evolved to specifically recognize, target, and eliminate cells harboring foreign components. Therapies rejected by the body’s immune response lose efficacy and can cause severe toxicity—even death. The company’s solution is to avoid immunogenicity and DNA alterations altogether by leveraging naturally occurring editing systems already present in human cells – and allow those cells to read the correct genetic code and express the right protein, thereby fixing the disease.
In 2019, ShapeTX announced a $35.5M Series A financing, led by New Enterprise Associates (NEA), with additional participation from CureDuchenne Ventures.
Shape Therapeutics’ Scientific Advisory Board Members:
George Church, Ph.D.
George Church Ph.D., world-famous geneticist, molecular engineer, and chemist. He developed the methods used for the first genome sequence & million-fold cost reductions since, as well as pioneered many of the CRISPR advances in genome editing. He is currently a Professor of Genetics at Harvard Medical School and Professor of Health Sciences and Technology at Harvard and the Massachusetts Institute of Technology (MIT). He is Director of the U.S. Department of Energy Technology Center and Director of the National Institutes of Health Center of Excellence in Genomic Science. He has received numerous awards, including the 2011 Bower Award and Prize for Achievement in Science from the Franklin Institute and election to the National Academy of Sciences and Engineering.
James Collins, Ph.D.
James Collins Ph.D., is one of the pioneers of the field of synthetic biology and has made multiple synthetic biology and bioengineering breakthroughs in biotechnology and biomedicine. He serves as the Termeer Professor of Medical Engineering & Science and Professor of Biological Engineering at MIT, as well as a member of the Harvard-MIT Health Sciences & Technology Faculty, and core member of the Wyss Institute. His many awards include a Rhodes Scholarship, a MacArthur “Genius Award,” a National Institutes of Health Director’s Pioneer Award. Jim is also an elected member of the National Academy of Sciences, the National Academy of Engineering, the National Academy of Medicine, the American Academy of Arts & Sciences, as well as a charter fellow of the National Academy of Inventors.
Don Cleveland Ph.D.
Don Cleveland Ph.D. is an award-winning inventor and pioneer in the field of Antisense Oligonucleotide (ASO) and their uses in gene therapy. He was recently awarded the Breakthrough Prize in Life Sciences for his work on the pathogenesis of disease and ASO-mediated treatment approaches in ALS and Huntington’s disease. Don is currently Professor of Medicine and Department Chair of Cellular and Molecular Medicine and Neurosciences at the University of California at San Diego, and Head, Laboratory for Cell Biology at the San Diego branch of Ludwig Cancer Research. He has made pioneering discoveries on the mechanisms of chromosome movement and cell-cycle control during normal cellular division, as well as the principles of neuronal cell development and the relationship to defects that contribute to inherited neurodegenerative disease.
About Shape Therapeutics, Inc.
Shape Therapeutics, Inc. is creating the world’s leading RNA and protein targeting platforms focused on the cure of human diseases. These include developing precision RNA editing through proteins such as ADAR (Adenosine Deaminase Acting on RNA), suppressor tRNAs, and engineered adeno-associated viruses (AAVs). The RNAfix™ technology allows for the editing of RNA using natural human cellular machinery, limiting the risk associated with immunogenicity, cellular toxicity, or off-target DNA editing. The team’s founders include Prashant Mali, Ph.D., Francois Vigneault, Ph.D., and John Suliman. ShapeTx is headquartered in Seattle, Washington, with a satellite site opening in Cambridge, Massachusetts.
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