Scientific RNA Technology Enables Groundbreaking Discovery In Cancer Research
Cancer Genes and Chemotherapy
Thermo Fisher Scientific Inc. announced that the University of Texas Southwestern Medical Center has made a groundbreaking discovery using the company's Dharmacon RNA-interference reagents, marketed under the Thermo Scientific brand.
Dr. Michael White, professor of cell biology at UT Southwestern, and his team have identified 87 genes that appear to affect the susceptibility of human cancer cells to certain chemotherapy drug treatments.
RNA interference (RNAi) is a mechanism of gene regulation in which double- stranded RNA can "silence" a gene by eliminating the messenger RNA (mRNA) corresponding to that gene. Dr. White used the Dharmacon siARRAY(R) Whole Human-Genome collection of SMARTpool small-interfering RNA molecules, which target the entire human genome of more than 21,000 individual genes, to block the action of specific genes in isolated lung cancer cells. He found that when certain genes were silenced, the chemotherapy drug paclitaxel (Taxol) was dramatically more effective in destroying the cancer cells. Dr. White's study appears in the April 12 edition of the leading science journal, Nature.
This discovery could lead to the development of new drugs that target the protein products of the genes identified by Dr. White's team and enhance the effectiveness of current cancer therapies. The eventual result could be new combination therapies that lower the dose of chemotherapy, reducing its debilitating side effects.
"We are very pleased to have provided Dr. White and his team with our unique genome-wide collection of highly effective siRNAs," said William S. Marshall, Ph.D., vice president of technology and business development for biosciences at Thermo Fisher Scientific. "Dr. White's seminal work reported in Nature is an example of paradigm-shifting technology applied to a significant medical problem."
The Dharmacon siARRAY library enabled Dr. White's discovery because it allows scientists to quickly test how cells react when specific genes are silenced. This high-throughput technique employs small-interfering RNA (siRNA), the active intermediate in the RNAi mechanism. Dr. White and his team treated human non-small-cell lung cancer cells with siRNAs targeting each gene in the human genome and monitored survival in the presence or absence of the drug paclitaxel. They identified 87 different genes that, when inhibited, caused the cancer cells to be up to 10,000 times more sensitive to paclitaxel. Additional research will be needed to determine whether blocking the genes in pre-clinical and clinical studies has the same effect.
"Being able to do this in human cells - and being able to do it fast - is very powerful," Dr. White said. "The idea of the screen was to take advantage of new-generation technology to silence any gene we want. That's the power of a genome-wide screen - you go in without any expectations and let the data tell you what's important. We were very impressed by the potency and robustness of the Dharmacon siRNA collection, which is vital in enabling such large-scale screening efforts."
The University of Texas Southwestern Medical Center is a member of the RNAi Global Initiative founded by the RNA Technologies product team within Thermo Fisher Scientific. An alliance comprising 20 renowned not-for-profit biomedical research institutions from North America, Europe and Asia, the initiative provides a forum for members to share research protocols, establish experimental standards and develop mechanisms for exchanging and comparing screening data. UT Southwestern is the first institution to publish a human genome-wide study using the Dharmacon siRNA library.
"Dr. White is a founding member of the RNAi Global Initiative and the first to receive the whole genome siRNA collection," said Marshall. "Our goal in establishing the initiative was to combine the power of genome-wide RNAi- based screening with the collaboration of leading research institutions to accelerate biological and medical discovery. Dr. White has been a leader in our efforts."