Rabies Virus Helps Deliver Drugs into the Brainby Karen Vieira, MBA, PhD | January 6, 2008
One of the greatest challenges neurologists face is successful delivery of drugs to the brain. This is because a special filtering layer of tissue, called the blood brain barrier, protects the brain and spinal cord. The barrier acts like a molecular sieve, allowing only properly sized molecules through. This means that any medication needing to reach the brain (for example, to kill a brain tumor) needs to be small enough, and even then, it is difficult to target the drug to specifically reach the brain.
Kumar and his colleagues from Harvard Medical School have developed a potentially revolutionary drug delivery method, taking advantage of a known master infiltrator of the brain: the virus responsible for rabies, also known as the rhabdovirus. Rabies viruses travel from the site of infection (a local wound bite) to the nerves, through which it gains access to the brain. It is one of the few viruses known to be nearly 100% deadly to mankind, when vaccination has not been administrated. Kumar and colleagues took advantage of the virus’ neurotropic ability by isolating a protein from the viral outer layer used to bind to the brain cells. They then attached an experimental drug to the purified fragment of protein, a small-interfering RNA. This RNA-peptide complex showed highly specific ability to access neurons in the brain that expressed receptors to the neurotransmitter acetylcholine. This high specificity of drug action was demonstrated to only occur in the brain, and not in other tissues of the body.
In this study, the drug was injected into the tail of the mice, targeting the blood vessels. Using small interfering RNA (siRNA) as a drug treatment for many diseases has been powerfully successful in other animal models, but the problem has always been the process of making it a practical drug for clinical application. Therefore, this new technology developed by Kumar et al sheds light into a new, non-invasive and feasible way to deliver siRNA specifically to the brain.
siRNA is gaining popularity as a preferred drug treatment method since its early conception in the past seven years. It takes advantage of the cell’s ability to stop its own protein production as soon as a short RNA sequence corresponding to the protein is detected outside of the cell’s nucleus. This triggers a powerful protein synthesis arrest, which can be harnessed to modulate or treat diseases such as diabetes, Hepatitis C, and even transplant rejection.
In 2006 the discoverers of siRNA, Andrew Z. Fire and Craig C. Mello, won the Nobel Prize in Medicine.
Kumar, P. et al. Transvascular delivery of small interfering RNA to the central nervous system. Nature 448, 39-43 (2007).
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