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Forcing chromosomes into loops may switch off sickle cell disease
Date:8/14/2014

a milder form of the disease. "This observation has been a major driver in the field to understand the molecular basis of the mechanisms that control the biological switch, with the ultimate goal to reverse it," said Blobel.

In previous research, Blobel's team used bioengineering techniques to adapt zinc-finger proteins to latch onto specific DNA sites far apart on a chromosome. The chromatin loop that results transmits regulatory signals for specific genes.

In their current work, the scientists custom-designed zinc fingers to flip the biological switch in blood-forming cells, reactivating the genes expressing fetal hemoglobin at the expense of the genes expressing adult hemoglobin. The researchers achieved these results in cultured blood cells from adult mice and adult humans.

The next step, said Blobel, is to apply this proof-of-concept technique to preclinical models, by testing the approach in animals genetically engineered to have manifestations of SCD similar to that found in human patients. If this strategy corrects the disease in animals, it may set the stage to move to human trials.

In principle, added Blobel, the forced chromatin looping approach could also be applied to other hemoglobin-related disorders, such as certain forms of thalassemia in which elevated fetal hemoglobin levels might be beneficial.


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Contact: Rachel Salis-Silverman
salis@email.chop.edu
267-426-6063
Children's Hospital of Philadelphia
Source:Eurekalert

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