text: In order to replicate, viruses introduce their genetic material into the host cell, tricking the hosts cellular machinery into using it as blueprints for viral proteins. Retroviruses go a stage further by having their genetic material copied into the nuclear genome of the host cell. Scientists exploit this by substituting part of a viruss genetic material with therapeutic DNA or RNA. Like the genetic material (DNA or RNA) in viruses, therapeutic genetic material can be designed to simply serve as a temporary blueprint that degrades naturally, as in a non-integrative vectors, or to enter the hosts nucleus becoming a permanent part of the hosts nuclear DNA in infected cells.
  A number of viruses have been used for human gene therapy, including viruses such as lentivirus, adenoviruses, herpes simplex, vaccinia, and adeno-associated virus.
  Adenovirus viral vectors (Ad) temporarily modify a cells genetic expression with genetic material that is not integrated into the host cells DNA. As of 2017, such vectors were used in 20% of trials for gene therapy. Adenovirus vectors are mostly used in cancer treatments and novel genetic vaccines such as the Ebola vaccine, vaccines used in clinical trials for HIV and SARS-CoV-2, or cancer vaccines.
  Lentiviral vectors based on lentivirus, a retrovirus, can modify a cell's nuclear genome to permanently express a gene, although vectors can be modified to prevent integration. Retroviruses were used in 18% of trials before 2018. Libmeldy is an ex vivo stem cell treatment for metachromatic leukodystrophy which uses a lentiviral vector and was approved by the european medical agency in 2020.
  Adeno-associated virus (AAV) is a virus that is incapable of transmission between cells unless the cell is infected by another virus, a helper virus. Adenovirus and the herpes viruses act as helper viruses for AAV. AAV persists within the cell outside of the cells nuclear genome for an extended period of time through the formation of concatemers mostly organized as episomes. Genetic material from AAV vectors is integrated into the host cells nuclear genome at a low frequency and likely mediated by the DNA-modifying enzymes of the host cell. Animal models suggest that integration of AAV genetic material into the host cell's nuclear genome may cause hepatocellular carcinoma, a form of liver cancer.