Protein synthesis recoded

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PTCX ("Patch") platform

Our PTCX tRNAs are designed to overwrite errors in the genetic code known as “nonsense mutations” or “premature termination codons” (PTCs), which account for about 15% of single base pair mutations known to cause genetic diseases.

A natural STOP codon appears at the end of the mRNA coding sequence and signals that a complete protein has been synthesized. A PTC is a misplaced STOP codon within the mRNA coding sequence. Mutations cause PTCs to occur within the mRNA coding region and act like a period in the middle of a sentence by stopping the addition of amino acids. The result is a truncated protein with diminished or no function.

Overcoming PTCs

PTCs stop translation because there are no naturally occurring tRNAs that recognize their three-letter sequences (UAA, UAG, and UGA).

Our PTCX platform restores normal translation by engineering tRNAs bearing anticodons that are complementary to the UAA, UAG, or UGA STOP codons and incorporate the correct amino acid in the growing protein. For example, our Arg-tRNAUGA, reads a UGA PTC and adds the amino acid arginine.

Critically, engineered tRNAs do not interfere with naturally occurring STOP codons near the end of the mRNA. A well-established body of research demonstrates that multiple layers of control act at the end of an mRNA coding sequence to prevent tRNA readthrough and ensure termination of translation.

A universal tRNA-based drug platform

ACE tRNAs expand the potential of genomic medicine to improve the lives of patients across thousands of genetically defined diseases and cancer.

A particular ACE tRNA can target its corresponding PTC in any gene and anywhere within a given gene. The therapeutic implications of this versatility are profound, because the three PTCs account for about 15% of cases in thousands of genetically defined diseases. And in about half of those cases, the correct amino acid is arginine.

To rapidly drive drug development, we are considering the feasibility of basket trials across diseases caused by the same underlying nonsense mutation, which could lead to approval in multiple indications simultaneously. For example, once established as a treatment for hemophilia A, the same ACE tRNA would be readily adaptable to a host of other bleeding disorders.

Targeting cancer with our 
SWTX ("Switch") platform

We have engineered a variation on the PTCX platform that disrupts translation and interferes with cancer cell growth.

SWTX PLATFORM

Foundational papers and scientific publications 

Our science is rooted in the foundational research from the Ahern laboratory, which was the first to demonstrate that engineered tRNAs could be systematically screened for optimal therapeutic activity.  We have since built a robust and expanding discovery and drug development platform based on proprietary tools, information, and intellectual property.

These are key studies underlying our science and programs:

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