Rick,
Kmiec works for NPRO since late 2001.
Their going after sickle cell and huntington's.
Reproducing and measuring results have always
been stumbling blocks and they seem to imply
they've made progress. (there are two abstracts)
jmo - but NPRO's is just about broke and has to pay
ABT $20 million in May-04. They are out with
a press release stating they will sell their
paclitaxel business by Dec-03 - but I am wondering
to (a) who and (b) how much can they really get
for it - iow - I don't think a whole bunch.
Finally, with respect to Gary Taubes' article .....
here's the second abstract that will be presented ...
799. Regulation of Gene Repair Directed by Synthetic End-Modified Oligonucleotides
Li Liu,1 Erin E. Brachman,1 Miya D. Drury,1 Jenn M. Sonntag,1 Katie K. Maguire,1 Eric B. Kmiec.1
1Department of Biological Sciences, University of Delaware,
Newark, DE, United States.
Gene repair of genetic mutations offers the most direct and longlasting therapy for inherited diseases. While this emerging field evolves into the mainstream, the central issue remains the unstable frequencies of correction obtained in various cells and cell lines. We have now identified and manipulated the protein that regulates the assimilation of the oligomer into the target site, the rate-limiting step of gene repair. Once the ligonucleotide is hybridized to the target sequence, a mismatched base pair, created upon annealing, is repaired by the action of the cells’ inherent DNA repair pathways.
We now show that overexpression of the gene RAD51 elevates the repair frequency, if expressed during a specific phase of the cell cycle and at a controllable level. We have also created several superactivated Rad51 proteins containing up-regulated activity domains that can increase correction by 50 to 100 fold reproducibly.
Gene repair is also dependent on the rate of DNA replication, the strand of the helix targeted, and the status of histone acetylation at the chromosomal targeting site.
We routinely obtain between 1% and 5% gene repair, measured at the genotypic level and confirmed at the phenotypic level. Results from repair of the clinically-relevant ADA-SCID mutation and the DMD mutation will be discussed.
In contrast to the results obtained with synthetic oligonucleotides, we will report on the nonspecific, mutagenic activity of PCR fragments involved in a poorly-defined “process” of chromosomal insertion.
Taken together, we have defined the reaction parameters that form the basis of reproducible gene repair in eukaryotic cells and have successfully applied them to correct clinically-relevant targets.
208.164.121.55
Note:Can't provide a link but the minimum gene
repair % they need to 'fix' sickle cell is 11%
(from memory)
John |
