Antisense therapy, a magic bullet for the treatment of various diseases: Present and future prospectAntisense drugs are a new generation of gene-silencing
therapeutic agents with potential for targeted causal
treatment of as yet incurable diseases. Antisense therapy
is a form of treatment for genetic disorders or infections.
When the genetic sequence of a particular gene is known
to be causative of a particular disease, it is possible to
synthesize a strand of nucleic acid (DNA, RNA or a
chemical analogue) that will bind to the messenger RNA
(mRNA) produced by that gene and inactivate it,
effectively turning that gene "off". This is because mRNA
has to be single stranded for it to be translated.
Alternatively, the strand might be targeted to bind a
splicing site on pre-mRNA and modify the exon content of
This synthesized nucleic acid is termed an "anti-sense"
oligonucleotide because its base sequence is
complementary to the gene's messenger RNA (mRNA),
Abbreviations: ASO, Antisense oligonucleotides; CFTR, cystic
fibrosis transmembrane conductance regulator; ODN, antisense
which is called the "sense" sequence (so that a sense
segment of mRNA " 5'-AAGGUC-3' " would be blocked by
the anti-sense mRNA segment " 3'-UUCCAG-5' ").
Antisense drugs are being researched to treat cancers
including lung cancer, colorectal carcinoma, pancreatic
carcinoma, malignant glioma and malignant melanoma,
diabetes, Duchenne muscular dystrophy and diseases
such as asthma and arthritis with an inflammatory
component (Agrawal et al., 1995; 2000). Some of the
examples of antisense drug like fomivirsen (marketed as
Vitravene), has been approved by the US Food and Drug
Administration (FDA) as a treatment for cytomegalovirus
retinitis. Mipomersen (ISIS 301012) inhibits human
apolipoprotein (apo) B-100 synthesis and lowers
circulating apoB and low-density lipoprotein cholesterol