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

Scientists have altered key biological events in red blood cells, causing the cells to produce a form of hemoglobin normally absent after the newborn period. Because this hemoglobin is not affected by the inherited gene mutation that causes sickle cell disease, the cell culture findings may give rise to a new therapy for the debilitating blood disorder.

The novel approach uses protein-engineering techniques to force chromatin fiber, the substance of chromosomes, into looped structures that contact DNA at specific sites to preferentially activate genes that regulate hemoglobin. "We have demonstrated a novel way to reprogram gene expression in blood-forming cells," said study leader Gerd A. Blobel, M.D., Ph.D., who holds the Frank E. Weise III Endowed Chair in Pediatric Hematology at The Children's Hospital of Philadelphia. "If we can translate this approach into the clinic, this may become a new treatment for patients with sickle-cell disease."

Blobel and colleagues, including Wulan Deng, Ph.D., formerly a member of the Blobel laboratory, and current lab member Jeremy W. Rupon, M.D., Ph.D., published their findings online today in Cell.

Key to the researcher's strategy is a developmental transition that normally occurs in the blood of newborns. A biological switch regulates a changeover from fetal hemoglobin to adult hemoglobin as it begins to silence the genes that produce fetal hemoglobin. This has major consequences for patients with the mutation that causes sickle cell disease (SCD).

Fetal hemoglobin is not affected by this mutation. But as adult hemoglobin starts to predominate, patients with the SCD mutation begin to experience painful, sometimes life-threatening disease symptoms as misshapen red blood cells disrupt normal circulation, clog blood vessels and damage organs.

Hematologists have long known that sickle cell patients with elevated levels of fetal hemoglobin compared to adult hemoglobin have
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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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