Antisense technology prevents the production of
proteins involved in disease processes, which results in a therapeutic benefit
to patients. This area of the website provides basic scientific background for
understanding how antisense drugs are made and how they work. 
Basic Science
Proteins are fundamental components of all living cells and include many types
of molecules necessary for carrying out the body’s functions, such as
enzymes, hormones and antibodies. The overproduction or abnormal production
of proteins is implicated or associated with many diseases. The following paragraphs
explain the process of protein production and discuss how antisense prevents
undesirable protein production in disease.
Protein Production
Genes contain the information necessary to produce proteins. A gene is made
up of bases (Adenine, Thymine, Cytosine and Guanine commonly refered to as A,
T, C and G), which are linked together to form a two-stranded structure that
resembles a twisted ladder, known as DNA (deoxyribonucleic acid). The nucleotides
on one side of the ladder interact with complementary nucleotides on the other
side of the ladder according to specific rules (A pairs with T, C pairs with
G), creating the ladder’s rungs. This highly specific nucleotide binding
is called hybridization. The sequence or order of these nucleotides establishes
the cell’s recipe for making proteins.
One of the DNA strands is called the sense strand and the other is called the antisense strand. A segment of a DNA helix might have the following base pairing:
Protein production occurs in two phases called transcription and translation. In the transcription phase, the DNA strand is used as a template for the manufacturing of a RNA molecule. The RNA strand of nucleotides is complementary to the DNA sense strand with one exception: Uracil (U), instead of Thymine, is the base complementary to A. Messenger RNA (mRNA) is responsible for communicating the genetic message found in DNA to other areas of the cell so that protein production can take place. Unlike DNA, mRNA is single-stranded and able to leave the nucleus of the cell.
In the translation phase, the mRNA travels to the ribosome, which is the cell’s machinery that assembles proteins based on the instructions it carries.
Role of Antisense Technology
Antisense technology interrupts the translation phase of the protein production process by preventing the mRNA instructions from reaching the ribosome. Isis’ antisense drugs are short, chemically modified complementary nucleotide chains that hybridize to a specific complementary area of mRNA. Here’s an example:
When an antisense drug binds (hybridizes) to its target mRNA, the mRNA is degraded and therefore is not translated by the ribosome into a functional protein.
The mRNA is degraded through one of several mechanisms of action. One antisense mechanism frequently used to degrade the target mRNA is a natural enzyme called RNase H. RNase H is dispatched when a DNA-like antisense drug hybridizes to its target mRNA. RNase H finds this DNA-RNA hybrid and cleaves the target mRNA. The destruction of the mRNA inhibits production of the protein encoded by that mRNA. By inhibiting the production of proteins involved in disease, antisense drugs can create therapeutic benefits for patients.
At least 12 known antisense mechanisms can be induced once an antisense drug binds to its target RNA. Isis has created proprietary chemical modifications to exploit many of these mechanisms for drug discovery. As its understanding of these mechanisms further improves, the Company expects to develop antisense drugs with enhanced performance and for broader therapeutic applications.