Antisense Approaches in Analyzing the Functional Role of Proteins in the Central Nervous System - Drugs of Abuse: Neurological Reviews and Protocols - page 357

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Antisense Approaches in Analyzing the Functional
Role of Proteins in the Central Nervous System
John Q. Wang and Limin Mao
1. Introduction
Along with the emergence and development of the new fi eld of “proteomics,”
neuroscientists together with other life scientists have been offered the greater
opportunity to clone and sequence new biologically active proteins and to
assess alterations in protein expression at both mRNA and protein levels in
response to a variety of experimental manipulations (1) . As proteins serve as
important elements and molecules in cellular structures, receptors, transport-
ers, factors, enzymes, and so on, functional roles of these various proteins
largely determine cellular physiology. To assess the role of proteins, especially
receptors and enzymes, pharmacological antagonists/inhibitors have been used
as effective tools for decades. However, although these pharmacological tools
possess potent antagonistic actions, the selectivity against their specifi c targets
is relative and sometimes far from satisfactory. Moreover, the antagonistic
properties of these tools, which are usually characterized in vitro, may not be
refl ected in vivo. Lack of selective agents at all is another dilemma for analyz-
ing the function of some proteins, such as structural proteins, transcription
factors, and so forth.
Recent advances in molecular biology have led to the development of an
entirely new type of agents for analyzing functions of biological proteins.
This agent is a short, single-stranded DNA sequence, for example, antisense
oligodeoxynucleotide (2 , 3) , which is complementary to a selected region of an
endogenous mRNA encoding a specifi c protein. By binding to selected areas
of the target mRNAs in a sequence-specifi c manner, agents interfere with the
mRNA-directed translation and, as a result, prevent the synthesis of proteins.