Biotechnology company Prime Medicine has used the latest high-precision genetic engineering method, known as Prime Editing, for the first time to modify human DNA directly inside the body (in vivo). As part of an ongoing clinical trial, a patient with Wilson\u2019s disease has received the treatment. The company plans to publish preliminary results next year.<\/p>\n
Wilson\u2019s disease is a rare genetic disorder caused by a mutation in the ATP7B gene. This gene is responsible for producing a protein that removes excess copper from the liver. Without treatment, copper accumulates in the body, causing severe damage to the liver and nervous system, as well as neurological disorders. Using Prime Editing, scientists rewrote the DNA of liver cells to correct the faulty mutation.<\/p>\n
Why was Prime Editing needed?<\/p>\n
To date, the US Food and Drug Administration (FDA) has approved only one gene-editing therapy, Casgevy, for treating inherited blood disorders. It is based on the standard CRISPR\u2013Cas9 method, which is generally used to switch genes off completely rather than rewrite their sequences.<\/p>\n
Another method, Base Editing, can change individual \u201cletters\u201d of DNA, but it cannot correct the most common mutations in the ATP7B gene. This is why Prime Editing was chosen: it is a more complex and versatile system that can insert, delete and rewrite DNA segments with high precision.<\/p>\n
Editing Cells Inside the Body (In Vivo) and Outside It (Ex Vivo)<\/p>\n
The standard approach to date (ex vivo) involves removing cells from a patient, editing their DNA in laboratory conditions, and then returning them to the body. Prime Medicine has already tested a similar approach in two patients with a rare immune disorder. However, editing DNA directly inside the body (in vivo) is a much faster and less expensive process. In addition, ex vivo therapy often requires patients to undergo intensive chemotherapy to destroy unedited cells and allow the modified cells to multiply.<\/p>\n
On the other hand, the in vivo approach presents its own challenges:<\/p>\n
Delivery challenges: Gene-editing components are introduced into the body using tiny lipid particles, similar to those used in mRNA COVID-19 vaccines. According to Krishanu Saha, a biomedical engineer at the University of Wisconsin\u2013Madison, the main challenge is designing these particles so that they reach only the target organ without affecting other tissues.<\/p>\n<\/div>\n<\/div>\n<\/li>\n
Lack of prior verification: When cells are edited in a laboratory, specialists can check whether the changes were made correctly before returning the cells to the patient. With editing performed directly inside the body, such prior verification is impossible.<\/p>\n<\/div>\n<\/div>\n<\/li>\n<\/ul>\n
Other in vivo editing methods are currently being tested in clinical trials, including treatments for genetic disorders that cause high cholesterol and for alpha-1 antitrypsin deficiency, a condition that damages the lungs and liver. Meanwhile, the FDA is expected to decide early next year whether to approve an in vivo CRISPR\u2013Cas9 therapy for hereditary angioedema.<\/p>\n