Scientists at the Broad Institute of MIT and Harvard have demonstrated a third-generation CRISPR gene-editing technique capable of correcting single nucleotide errors in DNA with an accuracy of 99.97% — a level of precision that opens the door to treating thousands of genetic disorders previously considered beyond the reach of gene therapy.

The technique, known as base editing 3.0, uses a modified CRISPR-Cas9 protein fused to a deaminase enzyme to chemically convert individual DNA bases without cutting the double helix — avoiding the unintended mutations, known as off-target edits, that have complicated earlier gene-editing approaches.

"What makes this transformative is the specificity," said Professor David Liu, whose laboratory developed the technique. "There are approximately 32,000 known disease-causing point mutations in the human genome. In theory, base editing could address the majority of them."

Early clinical trials using previous versions of base editing have already produced remarkable results in patients with sickle cell disease, a blood disorder caused by a single faulty nucleotide. In a Phase I/II trial, all 16 patients treated showed complete or near-complete correction of the mutation, with no serious adverse events.

The new technique has been validated in cell culture and animal models for several additional conditions, including a form of familial high cholesterol that causes heart attacks in young adults, a severe immunodeficiency disorder that currently requires bone marrow transplants, and a rare genetic form of blindness.

Regulatory agencies in the United States and Europe are watching the technology closely. The FDA has granted three base-editing therapies 'Breakthrough Therapy' designation, which accelerates the review process for treatments that address serious conditions with unmet medical needs.

The cost of gene therapies remains a formidable barrier. The two CRISPR-based treatments currently approved for sickle cell disease are priced at between $2 million and $3 million per patient — far beyond the reach of healthcare systems in the low- and middle-income countries where sickle cell disease is most prevalent.

"We have the science to cure many of these diseases. The challenge now is an economic and political one," said Dr. Jennifer Doudna, who shared the 2020 Nobel Prize for the discovery of CRISPR. "How do we ensure that the benefits of this technology reach the people who need it most?"