Biology Reference
In-Depth Information
has been one of the great successes of recombinant DNA technology,
such as the use of recombinant cytokines for the treatment of cancers
and chronic viral infections. Yet it is clear that administering the gene
rather than the protein could have numerous advantages: proteins
synthesized
in situ
could avoid the toxicities associated with systemic
administration; administration of genes could mean that the protein
expression could persist for longer periods of time (compared to the
short half-lives of the recombinant proteins); and a protein synthe-
sized
in situ
would have appropriately mammalian post-translational
modifications, thus circumventing one of the major challenges that
can occur when producing recombinant proteins in non-mammalian
host cells.
DNA vaccines have further potential advantages as a product,
besides the immunologic and clinical issues noted above. The manu-
facturing process is relatively generic compared to either small mol-
ecule drugs or other biologicals such as either recombinant proteins
or live viral vaccines. DNA vaccines are bacterial plasmids, with the
differences generally being simply the gene insert and a promoter. So
the production process of growth in bacterial hosts and the subse-
quent purification of the plasmids is reasonably similar for different
vaccines or therapies, and the plasmids are easier to purify than
recombinant proteins. Moreover, DNA vaccines are more stable than
live viruses. Current embodiments of DNA vaccine include formula-
tions and delivery systems that may make them more complicated as
products,
3,4
but the generic nature of the entity remains a compelling
attribute.
Pre-Clinical Proof of Concept
The demonstration that DNA vaccines could work pre-clinically
in vivo
was done using a simple plasmid of DNA coding for a protein from
the influenza virus. That study showed that the DNA could result
in the generation of both cytotoxic T lymphocytes and antibodies,
and more importantly, could protect from an otherwise lethal chal-
lenge with a strain of influenza different from the strain from which
the gene had been cloned.
2
The ability to protect the animals in a
