A combination of two techniques promises to improve the efficiencyand effectiveness of experimental gene therapies, while alsoreducing potential side effects says a new research reportpublished in the December 2011 issue of the FASEB Journal . The report describes how scientists from Germany combined twotechniques involving the use of site-specific recombinases, orenzymes that facilitate the exchange of genetic material betweenDNA strands, to help guide exactly where new genetic material isinserted into a cell's DNA. This experimental approach to genetherapy represents an important advance, as successful gene therapyhas the potential to correct the root cause of numerous illnessesand health conditions. "The central outcome of these and related techniques is thepredictability and safety of a therapeutic regimen," said JuergenBode, a researcher involved in the work from the Institute ofExperimental Hematology at Hanover Medical School in Hanover,Germany. |
"These novel strategies will obviate the majority ofanimal experiments that are presently needed; it will enhance theeffectiveness and shorten the timeline." To make this discovery, Bode and colleagues identified two types ofsite-specific recombinases (SSR), one from yeast (Flp recombinase)and one from phages (PhiC31 recombinase), which are capable oftagging and targeting specific areas in a DNA strand. Specifically,the tagging process involves mounting a distinct address within agenome, whereas the targeting process covers the delivery ofgenetic material to this address. PhiC31was identified as an idealenzyme for tagging because it recognizes just a limited number ofpre-existent genomic addresses with well-known and mostlybeneficial characteristics, allows for only a one-way transfer ofgenetic material, and is basically irreversible. In contrast, Flprecombinase acts in a reversible manner, meaning that a giventarget can be modified over and over again to study the role ofslight changes in the structure of therapeutic proteins.
Althoughboth techniques have particular properties, they complement oneanother and may even be used in conjunction to obtain ultimateresults. "Successful gene therapy has been called the Holy Grail ofbiomedical research. It could revolutionize medicine as much, ifnot more, than the development of antibiotics ," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal . "While we have a long way to go, this report is an importantadvance. It shows us how to insert important genetic materialexactly where it is needed, rather than blindly popping it into acell and hoping for the best." Additional References Citations.
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