New editing technology precisely inserts gene-sized DNA, U.S. researchers say

A new gene-editing technology has been developed to insert long, gene-sized DNA fragments at precise locations in living human cells.

According to Azure Life Science on the 17th (local time), researchers at Boston Children’s Hospital announced a genome-engineering technology called “prime assembly” that day in the international journal Nature.

The technology expands on existing “prime editing.” Although precise, prime editing can make only small insertions, deletions and base substitutions, requiring hundreds of mutations to be corrected individually for each genetic disease.

By contrast, prime assembly can correct nearly all mutations within a gene in a single process. The method writes a new DNA flap at a specific location in the genome; the flap captures a DNA fragment with matching ends, turning it into a gene-sized insertion through permanent editing.

Co-senior author Daniel Bauer, director of the Gene Therapy Program at Boston Children’s Hospital, said, “Because it is based on prime editing, it has far fewer off-target effects than other gene-editing methods.”

Because the technology uses targeted insertion, it avoids the risk of toxicity that can result when the wrong gene is switched on and cause cancer. It also does not rely on DNA double-strand breaks or double-stranded donors, which can cause toxicity and cellular stress.

Unlike existing methods, which work mainly in dividing cells, prime assembly also works in nondividing cells. Dividing cells are rare in the body and more vulnerable to unwanted DNA changes.

The researchers plan to study the molecular mechanisms further to improve efficiency and precision. Bauer said, “We are improving ways to deliver prime assembly components to disease-relevant human cells, such as hematopoietic stem cells for treating blood disorders.”

He added, “We are also exploring several applications for delivering gene payloads as mutation-agnostic therapies to restore gene regulation in genetic diseases with unmet clinical needs.”