The Merkel lab is based in the Department of Pharmaceutical Sciences at Wayne State University, Detroit with a sister lab within the Department of Pharmacy at LMU Munich and focuses on novel non-viral and targeted nanosized siRNA delivery systems. We are especially
interested in local drug, gene, and siRNA delivery with an emphasis on pulmonary delivery for applications in cancer immunology and inflammatory diseases.
In 2006, Andrew Fire and Greg Mello were awarded the Nobel Prize in
Physiology for their discovery of gene silencing by introduction of
double-stranded RNA (dsRNA) (1). Their work led to the identification of a catalytic mechanism of a multi-protein complex (2) which incorporates short RNAs that on their part are complementary in sequence to mRNA which is subsequently degraded (1).
This mechanism can also be exploited biotechnologically. Long dsRNA which naturally or
directedly reach the cytoplasm are degraded by “Dicer”, an RNase
III-like enzyme, into small interfering RNAs (siRNAs) of 21 to 25
nucleotides in length (3).
After being transferred into the cytosol, where it is incorporated into
the RNA-induced silencing complex (RISC), double-stranded siRNA is
cleaved upon activation of RISC, and complementary mRNA can bind to the
antisense strand. Argonaute (Ago2), an endonuclease in the RISC,
subsequently cleaves the mRNA leading to down-regulation of the target
Since the discovery of an RNA interference (RNAi) mechanism in mammalian
cells, RNAi is routinely used in functional genomics and drug
development (4, 5). RNA based therapeutics, however, are rather sparse.
(1) Fire, A. et al., (1998) Nature 391, 806-11.
(2) Hammond, S. M. et al., (2001) Science
(3) Agrawal, N. et al., (2003) Microbiol
Mol Biol Rev 67, 657-85.
(4) Dorsett, Y. and Tuschl, T. (2004) Nat Rev Drug Discov 3, 318-29.
(5) Gomase, V. S., and Tagore, S. (2008) Curr Drug Metab 9, 241-4.
Prof. Olivia Merkel
Department of Pharmaceutical Sciences
Wayne State University