Flipping a Gene Switch Reactivates Fetal Hemoglobin, May Reverse Sickle Cell Disease

Scientists used a technique called forced chromatin looping in reprogramming gene expression in blood-forming cells, to manipulate key biological events in adult blood cells to produce a form of hemoglobin normally absent after the newborn period. Because this fetal hemoglobin is unaffected by the genetic defect in sickle cell disease (SCD), cell culture findings scientist examined may open the door to a new therapy for the debilitating blood disorder. Shortly after birth a biological switch flips during the production of hemoglobin. Regulatory elements in DNA shift the body from producing the fetal form of hemoglobin to producing the adult form instead. People with SCD undergo this transition, their inherited gene mutation distorts adult hemoglobin, forcing red blood cells to assume a sickled shape. Scientist genetically engineered zinc finger (ZF) protein, which they custom-designed to latch onto a specific DNA site carrying the code for fetal hemoglobin. This genetically altered protein is forced to attach to a protein that creates a chromatin loop, which activates gene expression that switch the body back to making embryonic hemoglobin. Doing this will cure people who have SCD, and with further research this can happen sooner than later.


A chromatin loop forms when an enhancer and a promoter, two widely separated elements in a DNA sequence, come into contact as they carry out gene activity.

http://www.sciencedaily.com/releases/2013/12/131208133646.htm