Drug Discovery Opinion

By far the majority of marketed drugs modulate the activity of proteins. Since the discovery of RNA interference (RNAi) over 10 years ago, a major goal has been to develop agents which will selectively block the synthesis of target proteins. Small interfering RNAs (siRNAs) occur naturally and are believed to have evolved as a defence mechanism against viral infection but synthetic siRNAs could potentially be used to silence any target gene. Although the idea is not conceptually difficult and many cancer-associated genes have been silenced in laboratory experiments, there have been a number of obstacles in developing RNAi for clinical use, not least of which is how to deliver the siRNAs to the target cells.

A team led by scientists and clinicians at the California Institute of Technology (Caltech) has now published the results of a small phase I clinical trial in patients with skin cancer showing that targeted nanoparticles can traffic into tumours and deliver siRNAs in a dose-dependent fashion when administered intravenously. The siRNA-containing nanoparticles used in the study are being developed by Calando Pharmaceuticals, Inc. and the technique used for detecting and imaging the nanoparticles inside cells from tumour biopsies was developed at Caltech. Although phase I studies are primarily designed as safety studies, the team was able to demonstrate that, in one patient who received the highest dose of nanoparticles, the target mRNA (M2 subunit of ribonucleotide reductase (RRM2)) had been cleaved at the predicted position and that protein levels had also been reduced.

Although more trials will be needed to show that such treatment is safe and effective, the study provides the first evidence that nanoparticles and RNAi can be combined to reduce expression of cancer-associated genes in human patients.

The results are published in the journal Nature.

Related posts:

1. New Target for Malignant Melanoma Malignant melanoma is the most aggressive form of skin cancer, involving malignant transformation of melanocytes. Although it is one of...
2. siRNA Experiments Identify Ebola Virus Drug Targets Antiviral drugs that exclusively target viral factors rather than host cell processes offer the possibility of fewer side effects but...
3. Clinical Applications of siRNA Quark Pharmaceuticals has recently announced that its partner Pfizer has begun a phase II clinical trial of a chemically modified...
4. Arsenic Gets Nanotechnology Treatment Despite its reputation as a poison, arsenic has long been used in Chinese medicine and, more recently, arsenic trioxide has...
5. Targeting ‘Normal’ Proteins to Kill Cancer Cells For the most part, cancer therapy has been aimed at exploiting pathways that are present in cancer cells and not...

Related posts brought to you by Yet Another Related Posts Plugin.

 Email This Post

This entry was posted on Wednesday, March 24th, 2010 at 8:33 am and is filed under News. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.