Genome editing using nanoparticle technology treats blood disorder

Researchers have developed a novel genome-editing technique to correct the defective gene that causes the blood disorder beta-thalassemia.

The team, from Carnegie Mellon University University and Yale University, inserted synthetic genetic material called peptide nucleic acids (PNA) into the stem cells of mice to remove the beta-thalassemia mutation. This led to long-term increases in haemoglobin that were sufficient to cure the disease.

'We have developed a system that uses FDA-approved nanoparticles to deliver our PNA molecule along with donor DNA to repair a malfunctioning gene in living mice. This has not been achieved with CRISPR,' said Danith Ly, professor of chemistry at Carnegie Mellon University.

Beta-thalassaemia is a blood disorder that reduces the production of haemoglobin and leads to a lack of oxygen throughout body, causing weakness, fatigue and serious complications.

The research team designed a PNA molecule genome-editing technique specifically to target the gene associated with haemoglobin production. Using an FDA-approved vehicle, PNAs and a strand of healthy donor DNA encoding the haemoglobin gene were injected into the bone-marrow stem cells of live mice. By binding to the DNA target area, one strand of the mutant DNA was displaced and replaced by the healthy DNA, in turn engaging the cell's own DNA repair pathways and correcting the malfunctioning gene.

As reported in Nature Communications, successful genome editing was achieved in seven percent of cases, with elevated levels of haemoglobin evident for 140 days after treatment.

'The effect may only be seven percent, but that's curative,' Ly said. 'You don't need 100 percent to see the phenotype return to normal.'

PNA molecule genome editing provides a complex but efficient alternative to CRISPR. In binding to a specific area on DNA, it reduces the potential for mistakes in genome editing that are possible with CRISPR.

'[CRISPR is] so good at cutting the genome, it tends to make cuts at the wrong place, too. I think our technology is much harder to make, but we believe it's much more specific, with less off-target effects,' said Peter Glazer, a Yale University professor of genetics and co-author of the study.

Genome-editing enzymes used in CRISPR are also large and can only be used on extracted living cells, while PNA-mediated genome editing can be used in living animals because of the small size of the particles.

Despite these potential advantages, the PNA-mediated technique has yet to be tested in humans. 'That's the goal, to try to replicate this mouse model in humans,' Ly told The Washington Post.