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Biological breakthrough may lead to new treatments for sickle cell disease

Washington, Dec 09 : Researchers have manipulated key biological events in adult blood cells to produce a form of haemoglobin normally absent after the newborn period.


"Our study shows the power of a technique called forced chromatin looping in reprogramming gene expression in blood-forming cells," said hematology researcher Jeremy W. Rupon, M.D., Ph.D., of The Children's Hospital of Philadelphia. "If we can translate this approach to humans, we may enable new treatment options for patients."

Haematologists have long sought to reactivate fetal haemoglobin as a treatment for children and adults with sickle cell disease (SCD), the painful, sometimes life-threatening genetic disorder that deforms red blood cells and disrupts normal circulation.

In the normal course of development, a biological switch flips during the production of haemoglobin, the oxygen-carrying component of red blood cells. Regulatory elements in DNA shift the body from producing the fetal form of haemoglobin to producing the adult form instead. This transition occurs shortly after birth.

When patients with SCD undergo this transition, their inherited gene mutation distorts adult hemoglobin, forcing red blood cells to assume a sickled shape.

The researchers used a specialized tool, a genetically engineered zinc finger (ZF) protein, which they custom-designed to latch onto a specific DNA site carrying the code for fetal hemoglobin.

They attached the ZF to another protein that forced a chromatin loop to form. The loop then activated gene expression that produced embryonic hemoglobin in blood-forming cells from adult mice.

The team obtained similar results in human adult red blood cells, forcing the cells to produce fetal hemoglobin.

The study was presented at the annual meeting of the American Society of Hematology (ASH) in New Orleans.

--ANI (Posted on 09-12-2013)

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