Gene therapy gets under the skin
Vaseline, a known molecule from apples and a gene network encapsulated in algal gelatin are the components of a possible gene therapy which literally gets under the skin. This is what a research group in the Department of Biosystems (D-BSSE) in Basle managed to achieve.
“An apple a day keeps the doctor away”. This English proverb now has a new meaning. Marc Gitzinger from the research group of Martin Fussenegger, Professor of Biotechnology and Bioengineering Science in the Department of Biosystems (D-BSSE) in Basle, has developed a prototype for gene therapy through the skin. An important part in this is played by phloretin, an antioxidant found in apples which makes cell walls more permeable and is used in cosmetics as an anti-wrinkle agent. The researchers have presented their new therapeutic approach online in the current edition of PNAS.
Capsules and cream
The method of administration sounds very simple: first implant a capsule with a particular gene under the skin and then apply skin cream in order to stimulate the gene into action, which finally expresses an active principle which is able to escape from the capsule in a precise dose.
Fussenegger’s group has managed to do something which sounds like science fiction. The researchers have produced alginate capsules with living cells containing a specially designed genetic network. This network produces the protein SEAP. The capsules were implanted under the skin of test mice which were then coated with an ointment. This skin cream consists of commercial milk fat mixed with phloretin according to a particular formula.
And it worked. Phloretin penetrated the skin, the gel capsules and the cells contained within. As hoped for by the researchers, the antioxidant from the apples reduced the production of protein. With a large dose of phloretin in the cream, the production of SEAP could be stopped altogether.
“When developing the principle we had no particular clinical picture in mind”, emphasised the ETH professor. “We were concentrating on the route of administration through the skin”. A genetic network such as this can also be designed in such a way that when activated correctly, insulin or growth factors are produced. The researcher can imagine that certain metabolic diseases might be treatable by this method. The D-BSSE scientists have already had the method patented and hope that the pharmaceutical industry will be interested in further developing this principle.
This form of gene therapy has several advantages, stressed the ETH professor. It puts no strain on the liver because it has a very local action and phloretin is a molecule which can be found in everyday foodstuffs and undergoes rapid degradation in the body. Furthermore, the network can be precisely controlled and the therapy is well tolerated by the liver, adds Fussenegger. The disadvantage of orally administered therapeutic agents is that the liver, as the detoxifying organ, destroys most of the active agent before it reaches the target site.
Fussenegger is also convinced that implants are well accepted by the public. Implants can be stored in the body for a relatively long time and are easily removed after the end of therapy or in the event of complications.
This new genetic network is a typical example of progress in synthetic biology. Researchers use known and well-characterised biological components to construct artificial networks which in turn are able to produce gene products such as specific proteins. Researchers can also use certain components to make biological switches which in turn allow such systems to be switched on or off.
Gitzinger M, Kemmer C, El-Baba MD, Weber W, Fussenegger M. Controlling Transgene Expression in Subcutaneous Implants Using a Skin Lotion Containing the Apple Metabolite Phloretin. PNAS, online publication 22 June 200. doi:10.1073/pnas.0901501106