Cancer genes switched off in humans

Cancer genes switched off in humans
ANI,Mar 22, 2010, 12.59pm IST
Forthe first time, researchers have used short sequences of RNA that caneffectively treat skin cancer in people by silencing specific genes behindtumour production.
Mark Davis from the California Institute ofTechnology in Pasadena and his colleagues have used the technique, called RNAinterference (RNAi), to deliver particles containing such sequences to patientswith the skin cancer melanoma.
When analysing biopsies of thetumours after treatment, they found that the particles had inhibited expressionof a key gene, called RRM2, needed for the cancer cells to multiply.
The researchers created the particles from two polymers plus aprotein that binds to receptors on the surface of cancer cells and pieces of RNAcalled small-interfering RNA, or siRNA, designed to stop the RRM2 gene frombeing translated into protein.
The siRNA works by sticking to themessenger RNA (mRNA) that carries the gene’s code to the cell’s protein-makingmachinery and ensuring that enzymes cut the mRNA at a specificspot.
When the components are mixed together in water, they assembleinto particles about 70 nanometres in diameter. The researchers can thenadminister the nanoparticles into the bloodstream of patients, where theparticles circulate until they encounter ‘leaky’ blood vessels that supply thetumours with blood.
The particles then pass through the vessels tothe tumour, where they bind to the cell and are then absorbed. Once inside thecell, the nanoparticles fall apart, releasing the siRNA. The other parts of thenanoparticle are so small, they pass out of the body in urine.
“Itsneaks in, evades the immune system, delivers the siRNA, and the disassembledcomponents exit out,”
When researchers analysed tumour samples from threeof the patients who volunteered samples, they found fragments of the mRNA inexactly the length and sequence they would expect from the design of theirsiRNA.
And in at least one patient, the levels of the protein werelower than they were in samples of the tumours taken before treatment.
They also found that patients who were given higher doses had higherlevels of siRNA in their tumours. “The more we put in, the more ends up wherethey are supposed to be, in tumour cells,” said Davis.
Davis saysthat by targeting specific genes he hopes these treatments will not have majorside effects. “My hope is to make tumours melt away while maintaining a highquality of life for the patients. We’re moving another step closer to being ableto do that now,” he said.
The study has been published in

Source