Sartorisu-Sowmya eBook - 18

DECIPHERING THE IMMUNE RESPONSE TO VIRAL INFECTION

Center, and W.W. Smith Charitable Trust Professor in Cancer
Research at the Wistar Institute. Weiner, a pioneer in the field,
said several key innovations are driving the new resurgence of
interest: "First, we can now engineer inserts into DNA plasmids
that will result in 25-50 times more protein expression per cell.
Second, we've learned to increase DNA formulations that also
have reduced volume. Third, we've dramatically increased our
delivery with advanced electroporation-assisted devices that
provide for cellular update of plasmid more than 1000-fold as
compared to plasmid delivery alone."
A search on clinicaltrials.gov revealed 610 current clinical
trials using DNA vaccines for the treatment of cancers, influenza,
and infectious diseases. Weiner feels that DNA vaccines provide
a valuable immunotherapy especially for rapidly emerging
infectious diseases. He gave the example of Zika virus. "During
the 2015 outbreak, there were no drugs and no vaccine
available to treat Zika," he recalled. "Our vaccine, a synthetic
DNA cassette featuring a Zika-specific antigen, was the first

18 | GENengnews.com

into the clinic and took only about 6.5 months to develop from
bench to bedside."
However, Weiner and colleagues have also taken another
approach to fighting Zika. They have engineered designer
synthetic plasmids with a DNA-encoding mAb, ZK190, that
can produce a full-length functional antibody known to
potently neutralize Zika in animal studies. The team found
that when delivered in vivo, the DMAb-ZK190 was produced
in the living animal and proved protective to Zika challenge in
both mice and rhesus macaques. Weiner explained, "Unlike
viral vector platforms, this platform is nonlive, nonintegrating,
and noninfectious while promoting rapid and transient highly
targeted DMAb generation."
Weiner sees a broad horizon for DNA platforms, from
fighting emerging infectious diseases to attacking cancer. "As
improvements continue to broaden our scope and accelerate
the pace of success," he says, "it is possible we are entering the
'Designer DNA Vaccine and Immunotherapy Era.'" n
http://www.clinicaltrials.gov http://www.GENengnews.com
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