ShapeTX is developing a new generation of Gene Therapies for some of the most daunting genetic diseases in the world. Our proprietary RNA technologies leverage machinery already present in human cells to safely and efficiently correct genetic mutations, while avoiding immunogenicity and DNA damage. This process will provide safer treatments that work with the body, not against it. We believe the cure is in you, we let biology reveal the way.
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. Our solution is to avoid immunogenicity and DNA alterations altogether by leveraging naturally occurring editing systems already present in our cells. The proprietary therapeutics we’ve created allow cells to read the correct genetic code and express the right protein, thereby fixing the disease.
For diseases generated by point mutations, we employ RNAfix™, a fit-for-purpose modified gRNA (guide RNA) that’s designed to recruit ADAR—a naturally occurring enzyme editor found in all human cells—to change how a single letter is read and subsequently expressed as a protein. Enabling a targeted RNA edit using ADAR can serve to correct mutations or purposefully create them to treat a vast array of genetic disorders. RNAfix™ can be used to induce A-to-G correction of point mutations, knockdown protein expression, induce exon-skipping, as well as modulate protein-protein interactions. RNAfix™ payloads can be gene encoded into AAV vectors or administered directly as chemically-modified RNAs, enabling flexible delivery and optimal efficiency. ShapeTX is currently pursuing both delivery approaches in various indications.
For diseases caused by premature stop codon mutations, we employ RNAskip™, a proprietary suppressor tRNA specifically engineered to recognize premature stop codons and enable translational readthrough to produce a fully corrected protein. There are only three genetically-possible premature stop codon sequences, making our suppressor tRNA therapy re-deployable across genetics disorders.1 RNAskip™ payloads can be gene encoded into AAV enabling long term duration of our therapy.
Innovative payloads require innovative delivery tools. Currently, many available Adeno Associated Viruses (AAVs) across the industry are plagued with severe limitations. From low tissue specificity, pre-immune exposure to poor manufacturing, AAV needs to be as advanced as the payload it carries.
To address delivery challenges, we built our AAVid™ capsid discovery platform that yields industry-leading, next-generation AAVs with optimized delivery properties. Equal parts molecular engineering and data science, our purpose-built AAV vectors can be used to efficiently deliver both our RNAfix™ and RNAskip™ payloads—as well as other industry leading payloads—to disease specific tissues. By combining rational mutational targeting with cutting-edge DNA synthesis technologies, we’ve generated massive candidate capsid libraries with unique AAV variants in the billions per single campaign.
Blending our expertise in genetic engineering, cellular therapy, and biologics manufacturing, we’re reshaping what AAV manufacturing means for the distribution of life-changing drugs. Using a proprietary human stable cell line production technology, we’re rebuilding AAV manufacturing to break down the barriers that prevent gene therapies from reaching those who need them most. The final products are drastically improved in yield and quality as well as higher in culture density, meaning our RNA therapies do more with less. Our manufacturing platform will enable us to accelerate drug innovation, reduce common toxicities, and result in increased accessibility through reduced scale and cost of production.
VersatilitySeveral mutation types result from base substitutions, so our RNA therapies have wide coverage and application over thousands of diseases.
BiocompatibilityBy harnessing human systems from within, our therapies minimize the risk of immunogenicity and DNA damage, producing results in intractable diseases.
EverlastingOur payloads stay in the cell as long as the cells are alive, enabling one-time, long-term—if not permanent—treatment.
SustainabilityEfficient manufacturing enables higher-yield and lower dosage requirements, making Gene Therapy economically feasible over time.
Innovation + DataResults bring data, and data drives our decision-making process toward the development of new therapies.
Others carved the path for where we are today, but we carry the torch to new terrains. RNA targeting is at the forefront of a radically new way to treat a range of diseases. And we’re just getting started.
Discovery of tRNA
Discovery of AAV
Identification of suppressor tRNAs
CRISPR RNAs first described
ADAR first described
ADAR as a therapeutic POC
First clinical trial using AAV
First in vivo suppressor tRNA study
Programmable CRISPR Cas9. Congrats on the Nobel!
ADAR-oligo fusion POC
CRISPR-Cas9 editing with in human cells
First ex vivo CRISPR edited cells used to treat lung cancer
First AAV encoded ADAR editing in vivo.
ShapeTX is born
First endogenous ADAR editing using genetically encoded guide RNA only.