Delivery technology 'could speed up siRNA development'
an up-and-coming technology for switching off genes in the body
that could accelerate its use in drug development.
A US research team, lead by Kent Kirshenbaum, at New York University has worked on a novel peptoid transfection reagent designed to deliver siRNA - small interfering RNA - into cells.
Gene silencing techniques have come into the spotlight as an important tool to treat malfunctioning genes in the human body. A novel peptoid vehicle delivery could help develop the market for siRNA therapeutics, expected to account for approximately half of a $3.5bn market in 2010, with the remainder taken up by research reagents, according to market researchers Jain PharmaBioTech.
Peptoids have been shown to efficiently transfect natural human cells, as opposed to other methods being successful in culture systems where cells may not behave normally. A vehicle that can deliver genetic material in a 'real-life' setting is of the essence for clinical applications.
Peptoids belong to a family of peptide mimetic compounds, which can be composed of particular sequences of diverse units. Their modular synthesis allows for chemical modifications for further advancements.
Kirshenbaum believes RNAi is ready to be more widely used in clinical trials but sees the need to improve delivery, make them more effective.
Clinical trials of RNAi therapeutics to date have tended to involve routes of administration where it is relatively simple to get the drug in contact with its target tissue. For example, Alnylam Pharmaceuticals is developing a drug for respiratory syncytial virus (RSV) infection that is delivered by inhaler into the lung. Meanwhile Sirna Therapeutics - just snapped up by Merck & Co in a $1.1 billion (€830m) deal - is developing a drug delivered directly into the eye for a major cause of blindness.
"There is a lot of fundamental research in the implementation that will be carried out before we discover optimal routes for clinical procedures that will provide maximum benefit for patients," said Kirshenbaum.
A problem with RNA silencing has been the potential for "off-target" effects, where a gene with a similar sequence to the target gene has been repressed. Kirshenbaum will continue to develop their peptoid reagents to reduce the likelihood of "off-target" effects.
"This is one area in which we need a lot more basic research to understand more fully the scope of this problem," says Kirshenbaum.
Kirshenbaum's goal is to develop a scientific understanding of the relationship between transfection reagents' behaviour in a living system and their pysio-chemical characteristics.
"We are currently performing studies on the nature of thenano-particles that may be formed by the oligonucleotide/transfectionreagent complexes. We hope to develop a knowledge-base that will allow a more thorough ability to provide for the design of transfection reagents that will allow targeting of RNAi effects to specific locations within the body," concludes Kirshenbaum.
The researchers have described their method in a recent article in Molecular BioSystems (DOI: 10.1039/b603229j).
