Chemistry Reference
In-Depth Information
9
Platinated Oligonucleotides:
Synthesis and Applications for the
Control of Gene Expression
Vicente March รก n and Anna Grandas
9.1 Therapeutic Applications of Synthetic Oligonucleotides
The genetic information necessary for making a living organism is encoded in DNA
(deoxyribonucleic acid), a very large biopolymer associated with many copies of
several proteins in chromosomes. The individual units of DNA that contain the
instructions for producing proteins are called genes. However, the fl ow of informa-
tion from DNA to proteins is mediated by a different nucleic acid, mRNA (mes-
senger ribonucleic acid), which differs from DNA in that deoxyribose is replaced
by ribose and thymine by uracil. According to the central tenet of molecular biology,
the information encoded by DNA in genes is transcribed into information in RNA
(although in some cases, such as in retroviruses, information fl ows from RNA to
DNA), which in turn is translated into the functional protein.
The availability of molecules that specifi cally target either protein or DNA or
RNA sequences is essential for the treatment of diseases of genetic, viral or bacterial
origin and malignant tumours. In this respect, the extraordinary capacity for recogni-
tion of nucleic acids through hydrogen bonding between complementary bases may
allow the use of nucleotide-based molecules to control the expression of a particular
gene.
In 1978 Zamecnik and Stephenson reported for the fi rst time the use of small
nucleic acid fragments, called antisense oligonucleotides (AS-O), as therapeutic
