Using Viral-Mediated Gene Transfer to Study Depressive- Like Behavior - Viral Vector Approaches in Neurobiology and Brain Diseases - page 160

2 General Safety Issues

2.1 Governmental
Regulatory Bodies

Oversight of biosafety issues is becoming more complex with
evolving guidelines from regulatory agencies in each country and
the particular policies of each institution. In the USA, biosafety
falls under the oversight of institutions that range from the Centers
for Disease Control, the Food and Drug Administration, and even
local county boards of health. Conducting research is further com-
plicated by the fact that funding organizations have also established
regulations associated with specifi c types of research. For example,
the National Institutes of Health publishes guidelines for research
involving recombinant DNA; these guidelines impact NIH-funded
research programs that use viral vectors in experiments, and the
guidelines also stipulate that all research at the funded institution
follow the guidelines regardless of funding source.

2.2 Environmental
Health and Safety

Because viral vectors involve recombinant DNA technology, gene
transfer, and live animal experiments, they are regarded with great
sensitivity by investigators and regulators alike. The arm of the
NIH called the Offi ce of Biotechnology Activities has mandated
the creation of Institutional Biosafety Committees (IBCs). Funding
institutions in the USA use these committees, composed of
Principal Investigators, department chairs, biosafety offi cers, and
members of the public, for institutional oversight of recombinant
DNA research. Oftentimes, the IBC works in concert with the
institutional environmental health and safety department, since
safety and use of biologicals is assessed by each body. Deciding to
use a viral vector in one's research will require a detailed biosafety
plan that spells out how the specifi c vector is obtained or made, a
safety assessment, and the procedures for its use in in vitro and in
vivo applications. Furthermore, investigators are required to have
detailed exposure and spill mediation plans. For example, our labo-
ratory has used an amplicon-based Herpes Simplex Virus (HSV)
vector system for more than a decade. Since this HSV vector sys-
tem utilizes replication-defi cient helper virus for packaging the
viral particles in a specifi c cell line, we are required to use Biohazard
Safety Level (BSL)-2 precautions. Afterward, we carefully confi rm
that each batch contains no revertants that have regained replica-
tion competency using a plaque assay, and then that particular
batch of vector can be used under BSL-1 containment. In our
institution and at others that we have collaborated with, these
arrangements must be negotiated by the investigator and the IBC
prior to initiating use of the viral vector. Finally, the rules regarding
which types of personal protective equipment and procedures are
required for each type of viral vector during preparation, in vitro
experiments, and in animals depend on the type of virus and must
be taken carefully into consideration.