Stories about: DNA

Zeroing in on the fetal-to-adult hemoglobin switch and a new way to combat sickle cell disease

Normal red blood cell vs. sickle-shaped blood cell, which is found in sickle cell disease
Normal red blood cell vs. sickle-shaped blood cell.

It’s been known for more than 40 years that in rare individuals, lingering production of the fetal form of hemoglobin — the oxygen-transporting protein found in red blood cells — can reduce the severity of certain inherited blood disorders, most notably sickle cell disease and thalassemia. Typically, however, a protein called BCL11A switches off fetal hemoglobin production past infancy, but exactly how this happens has not been well understood until now.

In a new paper in Cell, researchers at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center have revealed how BCL11A controls the switch in the body’s production of fetal hemoglobin to adult hemoglobin. It does so by binding to a DNA sequence — made up of the bases T-G-A-C-C-A — that lies just in front of the fetal hemoglobin genes.

Another approach to curing sickle cell disease is already being evaluated in a new clinical trial at Dana-Farber/Boston Children’s. The novel gene therapy restores fetal hemoglobin production by genetically suppressing BCL11A, which prevents it from blocking fetal hemoglobin production. Learn more.

“Genetically modifying this TGACCA segment could be another possible strategy to cure sickle cell disease by blocking BCL11A’s ability to bind to this DNA site and switch off fetal hemoglobin production,” says Stuart Orkin, MD, senior author on the study.

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To monitor health, simply trip the ‘nanoswitches’

WATCH: DNA nanoswitches change shape in the presence of biomarkers. The shape change is revealed in a process called gel electrophoresis. Credit: Wyss Institute at Harvard University

“Nanoswitches” — engineered, shape-changing strands of DNA — could shake up the way we monitor our health, according to new research. Faster, easier, cheaper and more sensitive tests based on these tools — used in the lab or at point of care — could indicate the presence of disease, infection and even genetic variabilities as subtle as a single-gene mutation.

“One critical application in both basic research and clinical practice is the detection of biomarkers in our bodies, which convey vital information about our current health,” says lead researcher Wesley Wong, PhD, of Boston Children’s Hospital Program in Cellular and Molecular Medicine (PCMM). “However, current methods tend to be either cheap and easy or highly sensitive, but generally not both.”

That’s why Wong and his team have adapted their DNA nanoswitch technology — previously demonstrated to aid drug discovery and the measure of biochemical interactions — into a new platform that they call the nanoswitch-linked immunosorbent assay (NLISA) for fast, sensitive and specific protein detection. It’s described this week in the Proceedings of the National Academy of Sciences.

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