Science: The most "safe" gene therapy vector does not appear to be safe, with haemophilia patients suffering from liver cancer after treatment

For a long time, adeno-related viral vector (AAV) has been recognized as the most ideal gene therapy gene carrier because of its long-term latent in the human body without showing any obvious pathogenicity.
, however, there have been repeated warnings in recent years that this seemingly safe treatment may be fatal.
December 22nd, local time, Science published an article entitled "Liver tumor in gene therapy raises concerns about virus widely used in treatment" again confirming this view.
a gene therapy for type B haemophilia at Dutch biopharmaceutical company UniQure was halted by the FDA after the patient developed hepatocellular carcinoma after treatment, the u.S. Federal Reserve reported.
: 10.1126 / science.abg2917 is at the center of public opinion is a gene therapy based on the AAV5 virus vector, which has previously been awarded the fda breakthrough therapy title and the EMA awarded priority drug (PRIME) title.
from previous clinical data, the treatment is very effective.
2019, uniQure shared clinical data from Phase 2 of the therapy at the 27th International Society for Thrombosis and Hemostation (ISTH), showing that three patients had 54 percent of their normal FIX activity after 36 weeks of treatment, with an average of 45 percent of normal.
phase 3 clinical trial, which was put on hold, involved 54 patients.
At the 62nd annual meeting of the American Society of Hematology, UniQure shared initial experimental data showing that patients' FIX levels increased from ≤2 percent to 37.2 percent after 26 weeks of dosing, reaching the main end of the trial, and six months after receiving one-time gene therapy, severe patients appear to have turned into functional cures.
statement issued by UniQure, there is reason to believe that a potential disease in the patient's body could cause him to develop cancer.
, the liver cancer patient 25 years ago had been infected with hepatitis B virus and hepatitis C virus, and these viruses chronic infections are related to 80% of liver cell carcinoma.
, the more important question is whether AAV gene therapy is related to the event, or whether it contributes to the development of liver cancer in patients.
November 2020, Nature Biotechnology published a research paper entitled A long-term study of AAV gene therapy in dogs with hemophilia ades clonal expansions of transduced liver cells.
article mentioned that 10 years after the AAV gene therapy of nine hemophilia-type dogs, it was found that some of the therapeutic gene fragments carried by the AAV virus were integrated near the dog's chromosomes to control growth, suggesting a possibility of cancer.
, AAV blood disease gene therapy had shown a possible risk of liver damage.
2001, liver damage was reported in clinical trials of AAV2 (containing the FIX gene) conducted at Children's Hospital of Philadelphia, as well as in clinical trials of other types of AAV vectors.
David Lillicrap, a haemophilia researcher at Queen's University in Canada, said: "Although it may not seem reasonable to blame AAV gene therapy for the cancer, although the patient has been treated for short periods of time, AAV may be inserted into the DNA of his liver cells in a way that stimulates the faster growth of cancer cells if a slow-growing liver lump has been produced in the patient's body."
" may also be a shortcoming of the uniQure study, which does not exclude people with HCV and HIV in the past.
the company is working with the FDA to investigate the cause behind the incident, which is expected to be investigated in early 2021.
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