[tt] Rhabdovirus as gene therapy vector for the brain

[Hughes, James J.]

http://brainblogger.com/2008/01/06/rabies-virus-helps-deliver-drugs-into
-the-brain/

Rabies Virus Helps Deliver Drugs into the Brain

6th Jan 2008 

GNIF_Neuroscience.jpgOne 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.

Reference 

Kumar, P. et al. Transvascular delivery of small interfering RNA to the
central nervous system. Nature 448, 39-43 (2007).