Nanotubes in the Therapeutic Delivery of siRNA
Short-interfering RNA (siRNA) has been receiving much attention since RNA interference was first discovered in 1998 by Andrew Fire and Craig Mello. siRNA in short is a short double strand of RNA that plays a role in RNA interference (RNAi). Effectively, what they do is once in a cell they silence, or knockdown a certain part of a gene (the gene expression)
(Bhat, Ellestad, Wheatley, Warren, Holt, & Power,
within the cell.
|Figure 1: How siRNA gene therapy works |
Therapeutically, siRNA has great potential, though there are several obstacles to still overcome. Firstly, once in the organism, the siRNA complex is seen as a foreign substance and so the parts of the mononuclear phagocyte system (part of the immune system) attempts to break the siRNA down. Secondly, delivering the siRNA to the specific organs and/or cells where it is needed. Once through the cell membrane, the endosome pathways within the cell try to break down the siRNA. After all that, the siRNA still needs to be potent enough to accomplish the task of silencing the gene expression.
Figure 2: Structure of carbon nanotubes
To fix these issues, scientists have been working on novel methods to deliver the siRNA to cells.
This blog will look at only one novel method, therapeutic delivery using carbon nanotubes. Carbon nanotubes are structures made up of a single rolled sheet of graphite (so the carbons are all in rings, usually carbon-8 rings) and then capped on each end by more carbon rings (usually a mix of carbon-5 and carbon-8 rings, see Fig. 2)
(Harris, 2010). As with most technologies, there are advantages to it, but there are
some issues too. On the plus side, the
nanotubes act like an extension of a syringe, but on the nanoscale. They are able to directly pierce a cell membrane,
delivering the siRNA right into the cytoplasm of the cell. This directness means siRNA can be put
directly into the central nervous system, thus siRNA can be put right at the
loci of the brain (the reason that they want to put the siRNA there is that the
loci affected in many forms of neurogenic diseases) (Bhat,
Ellestad, Wheatley, Warren, Holt, & Power, 2011). The stability of the atom also helps make it a great candidate (Liszewski, 2011).
Figure 3: Carbon nanotubes
There have been difficulties. Some results have shown the gene knockdown has not corresponded to the amount of siRNA originally in the nanotubes delivering the siRNA. The theory to why this happened is that the siRNA is not being properly released within the cell, so nanotubes with increased detachment capabilities are being developed. (According to Kostas Kostarelos, Ph.D., professor in the Nanomedicine Laboratory, Centre for Drug Delivery Research, The School of Pharmacy, University of London.) Kostarelos has also talked of the challenge of the insolubility of carbon nanotubes in most buffer solutions. To increase the solubility of the nanotubes, scientists have coated them in amphiphilic molecules (lipids and polymers) and also functionalised the nanotubes with various chemical groups to increase water dispersibility
In conclusion, we can see the potential that siRNA has, and the potential of using nanotubes to deliver the siRNA to the targeted cells. This could be a solution to many neurological diseases, as well as some cancers. Hopefully in the years to come more research into this will come to success, so we might someday see the results.
For more information on nanotubes, follow this link: http://www.personal.reading.ac.uk/~scsharip/tubes.htm#Links
For a more extensive explanation on how siRNA works, follow this link (being Youtube there are even more relevent videos linked to that one):
Bhat, R. K., Ellestad, K. K., Wheatley, B. M., Warren, R., Holt, R. A., & Power, C. (2011). Age- and Disease-Dependent HERV-W Envelope Allelic Variation in Brain: Association with Neuroimmune Gene Expression. Retrieved March 17, 2012, from PLos ONE: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0019176
Harris, P. (2010, April 20). Carbon nanotube science and technology. (The University of Reading) Retrieved March 18, 2012, from A Carbon Nanotube Page: http://www.personal.reading.ac.uk/~scsharip/tubes.htm#Links
Liszewski, K. (2011, April 15). New Strategies Tackle siRNA Therapeutic Delivery Issues. Retrieved March 15, 2012, from Genetic Engineering & Biotechnology News: http://www.genengnews.com/gen-articles/new-strategies-tackle-sirna-therapeutic-delivery-issues/3626/?kwrd=Nanotechnology&page=1
Yang, Y.-L., Chang, W.-T., & Shih, Y.-W. (2011). Gene Therapy Using RNAi. In C. Kan, Gene Therapy-Developments and Future Perspectives (pp. 31-46). Rijeka, Croatia: InTech.