New Research - technical article

[john]

P53 mutations have known to be associated with poor prognosis. This team of researchers have actually modified genes to show they to create this condition.

Next hopefully, the mutated p53 gene can be corrected using gene therapy

Frontlines | RNA Interference Maintained in Stem Cells

Short hairpin RNAs (shRNAs) offer a new way to silence genes, courtesy of RNA interference (RNAi). A study from Cold Spring Harbor Laboratory, home of the discovery of the RNAi enzyme dicer, indicates that these RNAs can be more than "off" switches. Different RNA hairpins corresponding to the same gene can squelch expression to different degrees, modulating a phenotype in a controlled way by tagging messenger RNAs for destruction.

Greg Hannon, Scott Lowe, and their collaborators used a well-studied gene in a well-studied organism--tumor suppressor p53 in mice (M. Hemann et al., "An epiallelic series of p53 hypomorphs created by stable RNAi produces distinct tumor phenotypes in vivo," Nature Genetics, published online Feb. 3, 2003, www.nature.com). In mice with B lymphoma, they destroyed bone marrow, then reconstituted it from hematopoietic stem cells bearing any of several different shRNAs corresponding to parts of the p53 gene. Complete deletion of p53 is known to increase cancer aggression.

The results were striking: The greater the p53 silencing, the faster the cancer spread and killed. "Each sequence affects gene expression to a different extent. It is a kinetic issue, dependent upon the strength of the sequence as an inhibitor, and how easily the sequence can be accessed in the message," says Hannon. Of course, no one would want to hamper the protective function of normal p53 expression, but that wasn't the goal. "It was a proof of principle. We can apply RNAi to a stem cell ex vivo, put it back in the animal, and it retains the altered characteristics," Hannon adds.

--Ricki Lewis