AAV Integration Frequency Assessment Service
Adeno-associated virus vector (AAV) integration frequency assessment plays a critical role in AAV vector biosafety evaluation in gene therapy. Using a number of technologies and scientific talent, Creative Biolabs provides comprehensive AAV integration frequency assessment service based on the value of quality first and time-saving.
Background of AAV Integration Frequency
Since the discovery in the 1960s and the advent of AAV vectors in the 1980s, the AAV vectors have revolutionized gene therapy in recent years. Investigations on AAV vector-based gene therapies have sprung up since the first AAV gene therapy product, named as alipogene tiparvovec, was approved by European Medicines Agency in 2012. The first product approved by Food and Drug Administration for in vivo AAV based gene therapy is voretigene neparvovec, and numbers of recombinant AAV gene therapy products for various diseases treatment are under clinical or pre-clinical phases at present.
As a small single-stranded DNA virus, AAV emerges as the predominant vector for therapeutic gene transfer with high efficiency and specificity. Usually, wild-type AAV vectors integrate into the human chromosome 19 of the infected cells mediated by binding of the AAV Rep protein to the AAV DNA and a site in chromosome 19. This integration into the genome of host cells improves the efficiency of transduction and expression to a certain extent and is necessary for certain applications, but also brings adverse results such as mutations. Integration frequency is an evaluation method to characterize the risk of AAV vectors integrating into the genome of infected cells.
Figure 1. AAV integration into the human genome. (Gaj, 2016)
Service
Although the integration frequency of AAV vectors is much lower than lentiviral vector and adenovirus vector, the risk of integration is still high. Moreover, recombinant AAV vectors by removal of the Rep gene from AAV DNA have addressed unwanted integration. However, for those non-removal or other recombinant AAV vectors, integration is still sufficiently high to produce some necessary as well as unwanted integration. Therefore, considering integration frequency is of great significance for future biosafety analysis in gene therapy and clinical application, it is imperative to evaluate and quantify the AAV integration frequency.
Possessing a set of advanced gene therapy platform, Creative Biolabs provides extensive integration frequency assessment services for various AAV vectors. Assisted by the methods of linear amplification-mediated polymerase chain reaction (LAM-PCR) and deep sequencing, we offer in vivo AAV vector integration frequency assessment analysis. Other methods such as quantitative PCR two-thirds partial tissue excision also can be utilized for AAV vectors integration frequency estimation (Inagaki, 2008).
In light of the dominant role of AAV vectors in gene therapy, Creative Biolabs has been providing scientific support with a diversity of recombinant AAV products and their related services. Our experience and dedicated customer service will ensure that your best interests are looked after when you turn to us with your AAV vector-based gene therapy projects.
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References
- Gaj, T.; et al. (2016). Genome Engineering Using Adeno-associated Virus: Basic and Clinical Research Applications. Molecular Therapy. 24(3): 458-64.
- Inagaki, K.; et al. (2008). Frequency and spectrum of genomic integration of recombinant adeno-associated virus serotype 8 vector in neonatal mouse liver. Journal of Virology. 82(19): 9513-9524.
