CAMBRIDGE, Mass., Dec. 17, 2019 (GLOBE NEWSWIRE) -- LogicBio Therapeutics, Inc. (Nasdaq:LOGC), a genome editing company focused on developing medicines to durably treat rare diseases in pediatric patients, today announced it has entered into an exclusive license with Oregon Health & Science University (“OHSU”) to intellectual property rights owned by OHSU while also extending a sponsored research agreement (“SRA”) to explore methods for enhancing selective advantage of edited hepatocytes using pharmacological agents with the laboratory of Markus Grompe, M.D., professor at OHSU. The initial phase of the research program provided proof-of-principle of enhanced selective advantage for cells edited by GeneRide™ in pilot murine experiments. This extension phase will focus on translating the enhancement strategy to non-human primates, a critical step before clinical translation to future GeneRide candidates and other technologies. GeneRide™ is LogicBio’s proprietary promoterless, nuclease-free genome editing technology, which is designed to provide a stable therapeutic effect by harnessing homologous recombination to precisely integrate corrective genes into a patient’s genome and leveraging endogenous promoters to drive gene expression.

LogicBio is currently working primarily in disorders where patients can benefit substantially even when only a modest percentage of their cells are modified and begin expressing the corrective transgene introduced by GeneRide. The Company has found, however, that in some genetic contexts, integrating the transgene gives hepatocytes a naturally-occurring selective advantage over cells that have not been modified. Over time, the percentage of modified cells expressing that transgene rises, potentially leading to more robust patient benefits. This was observed in an experiment in which a murine GeneRide construct was introduced into mice with and without a functioning copy of the Mut gene (deficient in the pediatric disease methylmalonic acidemia) in the liver. The initial GeneRide integration frequency was less than 1% in both sets of mice. Over time, this percentage remained stable in heterozygous mice that naturally express Mut in the liver (Mut+/- in liver). However, the share of cells expressing Mut increased to approximately 25% over more than a year in the mice genetically deficient in liver Mut (Mut-/- in liver). This selective advantage could be attributed to improvements in mitochondrial function as a result of Mut expression and restoration of the deficient essential metabolic pathway. These data were presented at the 2019 American Society of Gene & Cell Therapy Annual Meeting and can be found on the LogicBio website at the following link:

The goal of the expanded SRA with OHSU is to refine the pharmacological approach to providing a selective advantage to gene modified cells even when the transgene does not naturally confer a selection advantage at the cellular level. One such method involves adding an element to a GeneRide construct that gives cells incorporating that element a selective advantage when patients are treated with an external approved pharmacological agent. This research could enable expansion of the GeneRide platform to address genetic disorders in which clinical benefit emerges only after a higher percentage of cells are modified and begin expressing the corrective transgene.

“We are excited to explore novel methods for enriching the number of cells expressing the therapeutic gene. Such methods could improve the likelihood that patients derive long-term therapeutic benefit from a single treatment. They could also expand the range of serious genetic disorders we can address with GeneRide.”

Markus Grompe, M.D., professor at OHSU

Dr. Grompe’s lab studies monogenic disorders, particularly metabolic liver diseases affecting children. He has focused extensively on the use of in vivo selection to enhance cell and gene therapies. Dr. Grompe received the E. Mead Johnson Award for research excellence from the Society for Pediatric Research in 2002. He retains an active clinical practice, focused on metabolic disease.