One of the key findings is that
naked viral DNA is more infectious and have a wider host range than the
intact virus. Human T-cell leukaemia viral DNA formed complete viruses
when injected into the bloodstream of
rabbits . Similarly, naked DNA
from the human polyomavirus BK (BKV) gave a full-blown infection when
injected into rabbits, despite the fact that the intact BKV virus is not
infectious . This
hazard is particularly relevant to the entire range
of virus-based gene therapy vectors and naked DNA vaccines under
development . Modifications
to viral genomes can have unexpected
effects on virulence and the host range .
The safety of gene therapy
vectors is unproven . The
hazards include both direct toxicities and
indirect effects (see Box 3) and there is a growing debate over the
potential for generating infectious viruses, and harmful effects due to
random insertion into the cellular genome ,
both of which are shared by
naked DNA vaccines. Recombinant DNA vaccines, in both the naked and intact
viral form, also tend to be more unstable and prone to recombination,
increasing the likelihood of generating new viruses .
A viral vaccine
made by deleting genes from the simian immuno-deficiency virus (SIV) was
found to cause AIDS in infant and adult macaques , raising serious
safety concerns over similar AIDS viral vaccines for humans.
Gene therapy vectors and naked
DNA vaccines can cause acute toxic shock reactions  and severe delayed
immunological reactions . Between 1998 and 1999, scientists from US
drug companies failed to notify the FDA about six deaths that had occurred
during clinical trials of gene therapy, the causes of which are yet to be
determined . Naked DNA can also trigger autoimmune reactions, in which
the body’s immune system attack and kill its own tissues and cells.
New research shows that any fragment of double-stranded DNA or RNA
introduced into cells can induce these reactions which are responsible for
many diseases . Examples of autoimmune diseases are rheumatoid
arthritis, insulin-dependent diabetes and Graves disease of the thyroid.
Many ‘spontaneous mutations’ are due to insertions of
transposable elements and other invasive DNA. Insertion mutagenesis is now
found to be associated with a range of cancers, including lung ,
colon  and
liver  cancers. Finally, unintended
modification of germ-cells may result from gene therapy and
Not as much is known concerning
naked RNA. It is to be expected that antisense RNA, like antisense DNA,
will have biological effects either in blocking the function of homologous
genes or genes with homologous domains. RNA may also be reverse
transcribed into complementary DNA (cDNA) by reverse transcriptase, which
is present in all higher organisms as well as some bacteria , to become
incorporated into the cell’s genome.
The direct uptake and
incorporation of genetic material from unrelated species is referred to as
horizontal gene transfer
, or gene transfer by infection, to
distinguish it from the usual vertical
gene transfer from parent
to offspring in reproduction.