A newly-developed minimally-invasive gene-editing system using nanotechnology successfully cured a genetic blood disorder in living laboratory mice, says new research published in Nature Communications.
The system relies upon peptide nucleic acid (PNA) molecules, a synthetic neucleotide developed at Carnegie Mellon University. Made up of biocompatible nanoparticles containing PNAs, the system opens up DNA in order to bind near the target site.
“The nanoparticles are a critical component of this gene editing technology. It was developed by Dr. Mark Saltzman, a collaborator on this project. These nanoparticles are nontoxic and nonimmunogenic, already approved by FDA for treatment of neurodegenerative diseases,” Danith Ly, professor of chemistry in Carnegie Mellon College of Science, told Controlled Environments exclusively.
The recent study tested the efficacy of this system by inserting the PNAs and nanoparticles combination into mice to target a malfunctioning gene in beta thalassemia. Beta thalassemia is a blood disorder that reduces the production of hemoglobin and can cause pale skin, weakness, fatigue, and more serious complications.
Mice treated with PNAs displayed elevated levels of hemoglobin several months after treatment. Additionally, there was 7% successful gene editing in hematopoietic stem cells.
“Unlike the CRISP/Cas gene editing system, which requires manipulation of cells ex vivo (in the test tubes or cell cultures) and then put them back into animals (or patients), we bypass this step and deli%ver the gene editing cocktail directly into mice (hopefully into patients in the future) through IV,” Ly continued. “Although our correction efficiency is low, only 4-7% compared to 30-40% for CRISP/Cas9 and other gene editing technologies, that fact that the off-target effect is extremely low (1 in less than 400,000 chance) and the cocktails (nanoparticles, gamma-PNA, and donor DNA) are nontoxic, we could give such a treatment to patients multiple times to improve the correction efficiency.”
The researchers hope that this therapy will be safe in people.
“The results so far from animal model are promising. This is only the beginning. The road to developing a molecular therapy for “curing” genetic diseases is a long road ahead, but it is a path worth pursuing,” Ly concluded.