Research on “Gene Therapy Topical Ointment” Continues
Recent siRNA research, led by Northwestern University’s Chair of Dermatology, Dr. Amy Paller, has inspired new hope for silencing the underlying mutation of EI (epidermolytic ichthyosis) and its changes to the skin surface.
So what exactly is siRNA?
siRNAs are small interfering RNAs (sometimes called silencing RNAs) that “interrupt” the expression of a specific gene. They can recognize even the tiniest genetic change specifically, and thus can distinguish a normal gene from an abnormal gene. As one might imagine, their discovery has caused a surge in biomedical research and drug development for a variety of diseases. Now, that surge has crossed paths with EI.
How can siRNA effect EI?
The blistering and thickening of skin seen in EI patients usually results from a change in a single letter of the DNA code (a mutation) that provides the codes for manufacturing keratin protein in the upper layers of skin. This single letter change leads to a protein product (a keratin) which is produced but does not function normally. In a dominant disease, both a normal and an abnormal gene and mRNA exist. However, siRNAs can identify the abnormal strands of messenger RNA (the intermediary between the mutant gene and the abnormal protein), bind to them, and prevent the altered gene from being translated into protein. Until now, the problem with siRNA has been getting it through the skin barrier, the outermost layer of the epidermis, and into the cells making the bad protein.
Enter: Dr. Amy Paller, her extraordinary medical research team, and the fascinating field of nanotechnology*.
Dr. Paller and her team have discovered that siRNA, attached to a “central 13 nm gold nanoparticle” can be rubbed into the skin in a simple topical ointment ! In 2012, her research was awarded a $75,000 grant by the 2012 FIRST Research Grant Program. As of late, "We've developed 3-dimensional models of EI skin in culture and have also grafted EI skin to mouse models. We have found some siRNAs that prevent the gene from being expressed, but are testing them to find the best one that affects the abnormal, but not the normal gene,” said Paller. Read the full article here.
How will members of FIRST benefit from this research?
This type of siRNA gene therapy holds promise for individuals with EI, as well as other dominantly inherited ichthyotic conditions. If such drugs can be delivered by topical application, that would be a great advance. FIRST is committed to providing the latest progress of this research, as well all related news and information. Please visit our site as frequently as possible for the most recent updates. We also invite you to join our email list.
*Nanotecnology.def: n. a technology executed on the scale of less than 100 nanometers, the goal of which is to control individual atoms and molecules, especially to create computer chips and other microscopic devices. http://www.scientificamerican.com/topic.cfm?id=nanotechnology