Are viral vectors recognized as a biosafety measure?

Viral vectors are among the most efficient Gene transfer vehicles for eukaryotic cells. Retroviral, adenovirus, and adeno-associated virus (AAV)-derived vectors are often used for genetic engineering. For a viral vector to be safe or even recognized as a so-called biosafety measure, it must not be an independent Infectivity which also precludes its ability to replicate. The inability to replicate is usually achieved by the targeted deletion of essential viral replication genes.

These defective virus functions in the vector must not be (at most weakly) replaced by endogenous Helper viruses be complemented in the recipient cell, as they otherwise enable further gene transfer by releasing infectious virus particles from infected host cells. This applies to all deletion-mutated viral vectors, e.g., AAV vectors are based on so-called satellite viruses. AAV are naturally replication-defective viruses and require the support of helper viruses such as adenoviruses, human cytomegaloviruses, or herpesviruses for replication in the nucleus of the host cell. Prevalence of these helper viruses is low in the host population in Germany and neighboring countries, a significant transfer of the viral vector by endogenous helper viruses cannot be assumed.

The Recombination Recombination of replication-defective viral vectors with a wild-type virus, which leads to the restoration of replication competence, should be excluded if possible in order to recognize viral vectors as a biological safety measure. The probability of such a recombination event is low, but can be reduced in DNA-based vectors by a low homology between the vector and wild-type virus genome.

Vectors are recognized as part of a biosafety measure if

1. whose genome is fully annotated,
2. they do not have a broad host range,
3. they do not have their own transfer system for prokaryotes, have a low cotransfer rate and low mobilizability,
4. they are virally replication-deficient in eukaryotic cells and this defect is not compensated by helper viruses that are widespread in the host population.