What is AAV based gene therapy?
By Rachel Newton
What is AAV based gene therapy?
Simply put, AAV is transformed from a naturally occurring virus into a delivery mechanism for gene therapy. The viral DNA is replaced with new DNA, and it becomes a precisely coded vector and is no longer considered a virus, as most of the viral components have been replaced.
What is AAV used to treat?
The first AAV-based gene therapy approved by the FDA in December 2017, Luxturna (developed by Spark Therapeutics), is used to treat people with an inherited retinal disease.
What is the difference between AAV and adenovirus?
Adenoviruses have a capacity of ~8.5 kilobases, high levels of protein expression, and transient gene expression. The onset of expression can occur as early as 16-24 hours after infection….Adenovirus vs. AAV.
| Adenovirus | AAV | |
|---|---|---|
| Gene Expression | Transient | Potentially Long Lasting |
| Target Cell’s Immune Response | High | Very Low |
How many AAV clinical trials are there?
AAV vectors have been administered in an estimated 250–300 clinical trials and have had a good overall safety record to date in human patients.
Is AAV lytic or lysogenic?
AAV Life Cycle In the presence of helper virus (adenovirus or herpesvirus), the lytic stage ensues. During this period, AAV undergoes productive infection characterized by genome replication, viral gene expression, and virion production.
What is an AAV capsid?
The protein shell (capsid) of Adeno-associated viruses (AAV) are presently the most promising delivery vehicles for various in vivo gene therapies. AAVs are non-pathogenic and, through past engineering efforts, have become safe due to their inability to integrate into and damage the genome of target cells.
What factors must be considered when choosing a vector for gene therapy?
Important parameters to be considered when choosing a gene therapy vector include: (1) size limitations for insertion of transgenes, (2) purity and titer of the vector, (3) transduction efficiency, (4) ability to infect dividing and/or quiescent cells, (5) long-term expression of transgenes, (6) integration into the …
Is AAV gene therapy safe?
AAV vectors are considered safe and usually do not insert their own genomes into the human genome. However, several studies in mice have shown that the genomic integration of AAV gene therapy vectors can cause liver cancer. Denise Sabatino and colleagues studied AAV gene therapy in nine dogs for up to ten years.
What can you say about the bioethical issues of gene therapy?
The idea of germline gene therapy is controversial. While it could spare future generations in a family from having a particular genetic disorder, it might affect the development of a fetus in unexpected ways or have long-term side effects that are not yet known.
