Developing therapeutics to treat devastating genetic diseases of the liver.
We are focused on using mutation-agnostic in vivo gene insertion.
Our approach to genome editing inserts a full, healthy copy of a gene responsible for disease and is therefore independent of the genetic mutations that cause the disease. In contrast, some approaches focus on altering the specific bases in a gene that drive disease, creating a need for a resource-intensive, near-custom approach to diseases where dozens if not hundreds of mutations can cause a disease.
To do this, we will initially use an ARCUS® nuclease developed by Precision BioSciences and studied by genetic medicine pioneer Dr. James Wilson at the GTP. This enzyme cuts the genome at the well-characterized PCSK9 site, which serves as the insertion site for the healthy copy of the gene.
Currently, we use adeno-associated virus (AAV) to introduce the gene encoding for the nuclease and, separately, the healthy copy of the gene responsible for the disorder. We continue to evaluate other technologies for introducing the meganuclease and may develop alternative approaches in the future.
We are focusing our efforts initially on gene editing for liver disorders, especially in children. Over 400 rare, monogenetic liver disorders have been identified, affecting 10,000 or more births each year in the United States and European Union. Most of these diseases arise in childhood and are characterized by significant morbidity and an overall mortality rate of 20%.
Only 15 drugs have been approved for rare liver disorders by the FDA in the past 20 years, meaning children suffering from these disorders have very limited therapeutic options.
We are currently developing gene editing approaches to treat ornithine transcarbamylase (OTC) deficiency, the most common urea cycle disorder in humans, citrullinemia type 1 (CTLN1), a second urea cycle disorder, and phenylketonuria (PKU), a metabolic disorder caused by a loss of function in the enzyme that metabolizes the amino acid phenylalanine.
iECURE is enabled by a foundational collaboration with Dr. James M. Wilson at the University of Pennsylvania’s Gene Therapy Program (GTP). The GTP is comprised of more than 300 experts in vector engineering, discovery, early-stage development, gene therapy and gene editing manufacturing. The GTP’s expertise forms the backbone of early R&D for iECURE, with the GTP’s team responsible for executing all preclinical development work.