To investigate what gene products (usually proteins) do inside cells, it is extremely useful to be able to inhibit their expression, either transiently or long-term.

Our work, along with work from other labs, presented a technique that is potentially useful to many labs in the investigation of gene product function. Historically the most-cited papers are often of this sort. (When I was a grad student it was the denaturing, discontinuous protein gel system of Laemmli, then Sanger's DNA sequencing.) What sets ours aside is that we also challenged the accepted dogma as to where in the cells the technology was working.

Yes. It describes the ability to use simple recombinant DNA constructs to effect RNA interference effects in mammalian cells, by expressing short interfering RNA (siRNA or shRNA) from within the cells.

To investigate what gene products (usually proteins) do inside cells, it is extremely useful to be able to inhibit their expression, either transiently or long-term. It had previously been difficult to do this in mammalian cells (including human cells), but recent advances, including ours, have made this not only possible but well on its way to becoming routine. In the future, this ability to very selectively antagonize the expression of only chosen genes raises possibilities for creating antiviral agents and other forms of therapeutics using RNA that is produced inside of recipient human cells.

  How did you become involved in this research?

We investigate intracellular pathways for expression of small, functional RNAs in eukaryotes, from yeast to man. The obvious potential for RNA interference, if it could be expressed along these pathways inside mammalian cells, drew us to attempt these experiments.

David R. Engelke, Ph.D.
Professor, Department of Biological Chemistry
University of Michigan
Ann Arbor, Michigan, USA