For the first time, US scientists have attempted to edit the DNA of cells inside a patient in order to permanently cure a disease that currently requires weekly intravenous therapy.
Scientists at Sangamo Therapeutics are using genome editing to insert a corrective gene into a precise location in the DNA of liver cells.
Ultimately, the doctors aim to enable patients’ livers to produce a lifelong and stable supply of the enzyme iduronate-2-sulfatase (IDS), which sufferers of mucopolysaccharidosis type II (MPS II) – also known as Hunter syndrome – lack.
“For the first time, a patient has received a therapy intended to precisely edit the DNA of cells directly inside the body. We are at the start of a new frontier of genomic medicine,” said Dr. Sandy Macrae, CEO of Sangamo Therapeutics.
To insert the corrective gene the team didn’t use the popularised CRISPR gene-editing technique, instead they used Sangamo’s zinc finger nuclease (ZFN) genome-editing technology.
In order to restrict editing solely to liver cells, the ZFNs and the corrective gene were delivered in a single intravenous infusion using AAV vectors that target the liver. The ZFNs entered the cells as inactive DNA instructions in a format designed only for liver cells to unlock.
Once “unlocked”, the ZFNs then identified, clung to and cut the DNA in a specific location within the albumin gene. Using the cells’ natural DNA repair processes, liver cells then inserted the corrective gene at the precise location.
“We cut your DNA, open it up, insert a gene, stitch it back up. Invisible mending,” said Macrae in an interview with Medical Xpress, “It becomes part of your DNA and is there for the rest of your life.”
Without IDS people with MPS II suffer debilitating buildup of toxic carbohydrates in cells throughout their body.
As a result, patients may suffer from frequent colds and ear infections, distorted facial features, hearing loss, heart problems, breathing trouble, skin and eye problems, bone and joint flaws, bowel issues and neurological problems.
Previously the treatment for this condition involved weekly infusions of enzyme replacement therapy (ERT), but for patients with MPS II within a day of receiving ERT, IDS can quickly return to near undetectable levels in the blood.
“Even with regular infusions of ERT, which has markedly improved functional health outcomes, patients endure progressive damage to heart, bones and lungs. Many patients with MPS II die of airway obstruction, upper respiratory infection or heart failure before they reach the age of 20,” said Paul Harmatz, M.D., a pediatric gastroenterologist and a principal investigator for the CHAMPIONS study at the UCSF Benioff Children’s Hospital Oakland, where the first subject in the study was treated.