Gene Editing Clinical Trial for PKU
Homology is conducting the pheEDIT clinical trial with investigational one-time gene editing product HMI-103 in adults with PKU. Gene editing is designed to make a permanent correction to the genome where there is a missing or mutated gene.
HMI-103 incorporates nuclease-free gene editing for PKU, which means it does not cut the DNA like other gene editing approaches. Instead, HMI-103 is designed to harness the body’s natural DNA repair process to insert a functional copy of the PAH gene directly into the genome. Once safety and efficacy are established in adults, we plan to initiate trials in pediatric patients.
Screening Period
The trial will include a screening period to ensure participants meet the eligibility criteria to enroll in the study.
Study Period
Following a single I.V. administration of HMl-103, participants will be observed periodically for 2 years.
Follow-Up Period
Participants will be seen less frequently for additional years.
How could HMI-103 potentially work in the body?
Step 1
A patient would receive a one-time I.V. administration of HMI-103 consisting of functional copies of the PAH gene with a liver-specific promoter surrounded by long DNA sequences homologous to a specific location in the genome (homology arms).
Step 1
A patient would receive a one-time I.V. administration of HMI-103 consisting of functional copies of the PAH gene with a liver-specific promoter surrounded by long DNA sequences homologous to a specific location in the genome (homology arms).
Step 2
HMI-103 is designed to target the cells in the liver, where PAH activity is required to metabolize Phe normally.
Step 3
HMI-103 is designed to enter liver cells and deliver the PAH gene to the nucleus. Through the natural DNA repair process of homologous recombination, in some cells the functional PAH gene could integrate into the genome at the exact location where it is needed.
Step 4
The integrated PAH gene could then create functional PAH protein. The un-integrated PAH genes form episomes that also create functional PAH protein. PAH metabolizes dietary Phe, potentially restoring the normal biochemical pathway.
Learn more about pheEDIT:
pheEDIT fact sheet (English)
pheEDIT fact sheet (Spanish)
PKU Gene Editing Fact Sheet (English)
PKU Gene Editing Fact Sheet (Spanish)
HMI-103 is not approved by the U.S. Food & Drug Administration (FDA) or any other regulatory agency.