In Nature today the authors describe the use of siRNA, short interfering RNAs, which are injected using nanothechnology and interfere with the replication of melanoma cells.
The authors state:
Therapeutics that are designed to engage RNA interference (RNAi) pathways have the potential to provide new, major ways of imparting therapy to patients. Long, double-stranded RNAs were first shown to mediate RNAi in Caenorhabditis elegans, and the potential use of RNAi for human therapy has been demonstrated by the finding that small interfering RNAs (siRNAs; approximately 21-base-pair double-stranded RNA) can elicit RNAi in mammalian cells without producing an interferon response4. We are at present conducting the first in-human phase I clinical trial involving the systemic administration of siRNA to patients with solid cancers using a targeted, nanoparticle delivery system. Here we provide evidence of inducing an RNAi mechanism of action in a human from the delivered siRNA. Tumour biopsies from melanoma patients obtained after treatment show the presence of intracellularly localized nanoparticles in amounts that correlate with dose levels of the nanoparticles administered (this is, to our knowledge, a first for systemically delivered nanoparticles of any kind).
In Nature News they state:
Now, Mark Davis from the California Institute of Technology in Pasadena and his colleagues have found a way to deliver particles containing such sequences to patients with the skin cancer melanoma. When analysing biopsies of the tumours after treatment, they found that the particles had inhibited expression of a key gene, called RRM2, needed for the cancer cells to multiply. Their research is published today in Nature1.
The researchers created the particles from two polymers plus a protein that binds to receptors on the surface of cancer cells and pieces of RNA called small-interfering RNA, or siRNA, designed to stop the RRM2 gene from being translated into protein. The siRNA works by sticking to the messenger RNA (mRNA) that carries the gene's code to the cell's protein-making machinery and ensuring that enzymes cut the mRNA at a specific spot.
When the components are mixed together in water, they assemble into particles about 70 nanometres in diameter. The researchers can then administer the nanoparticles into the bloodstream of patients, where the particles circulate until they encounter 'leaky' blood vessels that supply the tumours with blood. The particles then pass through the vessels to the tumour, where they bind to the cell and are then absorbed.
Once inside the cell, the nanoparticles fall apart, releasing the siRNA. The other parts of the nanoparticle are so small, they pass out of the body in urine. "It sneaks in, evades the immune system, delivers the siRNA, and the disassembled components exit out," Davis says.
At the same time NCI has introduced an major trial analysis and comparison tool which is described as follows:
NCI researchers last month unveiled a new online tool for clinicians and professionals who recruit people to join cancer clinical trials. The tool, called AccrualNet, is both a repository of information and a forum for professionals to exchange ideas about the challenges associated with developing and managing these important studies.
AccrualNet was introduced at the Cancer Trial Accrual Symposium, held April 29–30 in Bethesda, MD. The conference, hosted by NCI and the American Society of Clinical Oncology, attracted more than 350 leaders and representatives from organizations actively engaged in clinical trial recruitment.
Posts
