stochasticity

Slow stochastic transgene repression with properties of a timer
Clifford L Wang, Desiree C Yang and Matthias Wabl
Genome Biology 2006, 7:R47 (doi:10.1186/gb-2006-7-6-r47)

Thoughts/Implications/Summary
The ability to identify clonal populations exhibiting predictable repression kinetics is intriguing. This finding has implications in the context of retroviral-mediated gene therapy. In this paper the location of integration was associated with the decay kinetics observed. This phenomenon is most likely cell-type/individual dependent. It may be possible to screen cells during retroviral-mediated gene therapy for the kinetics of transgene repression and identify those cells bearing an integration event at a genomic position allowing for predictable/reproducible expression kinetics and selection of clones with a low probability of tumorigenicity. One could envision a scenario where cells are isolated from an individual, "corrected" by way of retroviral integration of the functional gene in question, clonal populations of cells are identified that exhibit predictable expression/repression kinetics with subsequent use of these cells to treat the individual. If in vitro expression/repression kinetics are exhibited in vivo then one could tailor a treatment plan based on these kinetics. (That is assuming that repression is an issue of concern in individuals undergoing gene therapeutic modalities to treat the disease in question. I am ignorant of the long-term prognoses of individuals undergoing these treatments...) As an aside, one could also monitor these cells for things such as aneuploidy.