Microarray Applications in Drug Discovery and Development - Microarrays have become a critical tool in pharmaceutical research and provide in-depth analysis of the genome. - BioPharm International


Microarray Applications in Drug Discovery and Development
Microarrays have become a critical tool in pharmaceutical research and provide in-depth analysis of the genome.

BioPharm International

Alan Dance
The year 2003 marked the completion of the first draft of the human genome sequence. We now find ourselves in the modern genetic era, trying to understand and utilize a previously unimaginable amount of biological information. Scientists have the daunting task of finding new ways to use the human genome sequence to improve drug discovery and development efforts and to find better ways to combat disease for the benefit of humanity.

GeneChip Probe Arrays are Manufactured Through a Unique Process, Using a Combination of Photolithography and Combinational Chemistry.
A key tool that has emerged to help scientists sort through these enormous genome sequences is the high density microarray. Invented in 1989 by Stephen P.A. Fodor and colleagues,1-3 microarrays opened up an entirely new world to researchers, and now afford scientists the ability to analyze gene expression for the complete coding content of the human genome in a single experiment. This objective analysis method enables scientists to discover the underlying genetics and associated biochemical pathways that are disrupted in a wide range of diseases, from cancer4-6 to multiple sclerosis.7 Across multiple disciplines, whole-genome expression analysis is helping scientists to stratify disease, predict patient outcome, and generate information that can be used to make better therapeutic choices.

While microarrays were initially used to study gene expression, the most recent generation of arrays now allows scientists to study genome-wide DNA sequence variation.8,9 These new tools for disease mapping studies10-15 deliver the most markers and highest resolutions available, and have already helped scientists pinpoint genes linked to diseases such as bipolar disorder,11 sudden infant death syndrome,12 and neonatal diabetes.13

Characteristics like high-data-capacity, reproducibility, and accuracy make Affymetrix' GeneChip arrays ideally suited for basic disease research. This technology has revolutionized drug discovery and development, as well. Pharmaceutical companies have adopted high-data-capacity microarrays in drug discovery research for applications such as target identification, target validation and pathway analysis, compound profiling, and toxicology studies. Additionally, the arrays are currently being used in dozens of clinical trials to profile patient genetic and genomic information for more effective treatments and improved therapies. From a scientific obscurity developed 15 years ago, microarrays have become a critical tool in pharmaceutical research and are providing a more in-depth analysis of the genome for improved drug discovery and development.

DRUG DISCOVERY AND DEVELOPMENT One of the first steps on the road to more efficient healthcare is developing better drugs to treat disease more effectively. GeneChip arrays are now being used by pharmaceutical companies to improve nearly every aspect of the traditional drug discovery and development process, including target identification, target validation, compound screening, lead optimization, and clinical trials.

Disease Pathway Identification Researchers use genome-wide expression profiling to generate hypotheses for complex disease mechanisms and to identify drug targets and their pathways. Additionally, microarrays for dna analysis have been used to discover the genetic basis of disease by mapping disease genes with whole-genome snp assays.10-15 the two platforms complement each other: gene expression arrays identify differentially regulated genes from related individuals and dna analysis arrays can validate those differences in mapping experiments.

Disease Pathway Validation Once a disease pathway is identified, researchers need to know that disrupting the pathway will actually affect the disease etiology. Using whole-genome expression profiling, scientists can understand a wide range of effects — desirable and undesirable — that result from disrupting a pathway. They are then able to better evaluate potential targets for drug design. Modern technologies, like small interfering RNA, are now being used to rapidly and specifically inhibit gene function, speeding up the exploratory process of validating useful drug targets. However, being able to affect many different genes quickly requires an equally efficient way to measure the downstream effects generated by those changes.16

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