Each person has two copies, or alleles, of almost every gene. Huntington’s disease (HD) results from an error in one copy of the Huntington gene. The normal copy (the non-HD allele) makes a functional form of the huntingtin protein, while the abnormal copy (the HD allele) makes a harmful form of the protein that contains too much of the amino acidglutamine. This mutant protein tends to form protein aggregates in some nerve cells in the brain. Whether these aggregates are part of the HD disease process, or are simply a result of this process, is not yet known. However, many nerve cells containing aggregates will die in the brains of people with HD.
As mentioned in the previous update, “Fast and Cheap”: siRNA in Gene Silencing, researchers have discovered a way of hindering messenger RNA (mRNA), the “middleman” in the process of converting DNA to protein: they use small interfering pieces of RNA (short interference RNA [siRNA]). This technique is called RNA interference (RNAi). (An important note: the central dogma of molecular biology states that DNA codes for the production of RNA [transcription], which then undergoes translation into proteins. (Please see diagram below.) For more information on genetics, click here. The siRNA recognizes the mRNA transcribed from the HD allele and, with the help of other molecules in the cell, destroys this mRNA. Hence, the defective copy of the gene cannot be translated into a harmful protein. The normal copy of the gene remains intact and continues to code for the normal huntingtin protein.
The researchers’ next challenge is delivering the siRNA to the degenerating nerve cells, which requires something (such as a harmless virus or virus segment) that can transport it across the blood-brain barrier. Once they find a suitable chemical or mechanism to carry the siRNA to the nerve cells, they may be able to begin using RNAi therapy to treat HD.
To read more about RNAi, please click here and here.
Fig AE-1: The central dogma of molecular biology The central dogma of molecular biology describes the flow of genetic information from DNA to RNA to protein. The tongue-in-cheek term “central dogma” -not to be confused with religious dogma- was coined by Francis Crick (of Watson and Crick, the two scientists who discovered the double helix structure of DNA).
Last Modified: 05/22/2009
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