Featured Research

from universities, journals, and other organizations

Newly discovered gene regulator could precisely target sickle cell disease

Date:
October 10, 2013
Source:
Dana-Farber Cancer Institute
Summary:
A research team has discovered a new genetic target for potential therapy of sickle cell disease. The target, called an enhancer, controls a molecular switch in red blood cells called BCL11A that, in turn, regulates hemoglobin production.

"Coupled with recent advances in technologies for gene engineering in intact cells, it could lead to powerful ways of manipulating hemoglobin production and new treatment options for hemoglobin diseases," said Orkin, a leader of Dana-Farber/Boston Children's who serves as chairman of pediatric oncology at Dana-Farber Cancer Institute and associate chief of hematology/oncology at Boston Children's Hospital.
Credit: 18percentgrey / Fotolia

A research team from Dana-Farber/Boston Children's Cancer and Blood Disorders Center and other institutions has discovered a new genetic target for potential therapy of sickle cell disease (SCD). The target, called an enhancer, controls a molecular switch in red blood cells called BCL11A that, in turn, regulates hemoglobin production.

The researchers -- led by Daniel Bauer, MD, PhD, and Stuart Orkin, MD, of Dana-Farber/Boston Children's -- reported their findings today in Science.

Prior work by Orkin and others has shown that when flipped off, BCL11A causes red blood cells to produce fetal hemoglobin that, in SCD patients, is unaffected by the sickle cell mutation and counteracts the deleterious effects of sickle hemoglobin. BCL11A is thus an attractive target for treating SCD.

The disease affects roughly 90,000 to 100,000 people in the United States and millions worldwide.

However, BCL11A plays important roles in other cell types, including the immune system's antibody-producing B cells, which raises concerns that targeting it directly in sickle cell patients could have unwanted consequences.

The discovery of this enhancer -- which regulates BCL11A only in red blood cells -- opens the door to targeting BCL11A in a more precise manner. Approaches that disable the enhancer would have the same end result of turning on fetal hemoglobin in red blood cells due to loss of BCL11A, but without off-target effects in other cell types.

The findings were spurred by the observation that some patients with SCD spontaneously produce higher levels of fetal hemoglobin and enjoy an improved prognosis. The researchers found that these individuals possess naturally occurring beneficial mutations that function to weaken the enhancer, turning BCL11A's activity down and allowing red blood cells to manufacture some fetal hemoglobin.

"This finding gives us a very specific target for sickle cell disease therapies," said Orkin, a leader of Dana-Farber/Boston Children's who serves as chairman of pediatric oncology at Dana-Farber Cancer Institute and associate chief of hematology/oncology at Boston Children's Hospital. "Coupled with recent advances in technologies for gene engineering in intact cells, it could lead to powerful ways of manipulating hemoglobin production and new treatment options for hemoglobin diseases."

"This is a very exciting study," said Feng Zhang, PhD, a molecular biologist and specialist in genome engineering at the McGovern Institute for Brain Research at the Massachusetts Institute of Technology (MIT) and the Broad Institute of MIT and Harvard, who was not involved in the study. "The findings suggest a potential new approach to treating sickle cell disease and related diseases, one that relies on nucleases to remove this regulatory region, rather than adding an exogenous gene as in classic gene therapy."


Story Source:

The above story is based on materials provided by Dana-Farber Cancer Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Daniel E. Bauer, Sophia C. Kamran, Samuel Lessard, Jian Xu, Yuko Fujiwara, Carrie Lin, Zhen Shao, Matthew C. Canver, Elenoe C. Smith, Luca Pinello, Peter J. Sabo, Jeff Vierstra, Richard A. Voit, Guo-Cheng Yuan, Matthew H. Porteus, John A. Stamatoyannopoulos, Guillaume Lettre, and Stuart H. Orkin. An Erythroid Enhancer of BCL11A Subject to Genetic Variation Determines Fetal Hemoglobin Level. Science, October 2013

Cite This Page:

Dana-Farber Cancer Institute. "Newly discovered gene regulator could precisely target sickle cell disease." ScienceDaily. ScienceDaily, 10 October 2013. <www.sciencedaily.com/releases/2013/10/131010142752.htm>.
Dana-Farber Cancer Institute. (2013, October 10). Newly discovered gene regulator could precisely target sickle cell disease. ScienceDaily. Retrieved September 23, 2014 from www.sciencedaily.com/releases/2013/10/131010142752.htm
Dana-Farber Cancer Institute. "Newly discovered gene regulator could precisely target sickle cell disease." ScienceDaily. www.sciencedaily.com/releases/2013/10/131010142752.htm (accessed September 23, 2014).

Share This



More Health & Medicine News

Tuesday, September 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Costs Keep Mounting

Ebola Costs Keep Mounting

Reuters - Business Video Online (Sep. 23, 2014) The WHO has warned up to 20,000 people could be infected with Ebola over the next few weeks. As Sonia Legg reports, the implications for the West African countries suffering from the disease are huge. Video provided by Reuters
Powered by NewsLook.com
Ebola Cases Could Reach 1.4 Million Within 4 Months

Ebola Cases Could Reach 1.4 Million Within 4 Months

Newsy (Sep. 23, 2014) Health officials warn that without further intervention, the number of Ebola cases in Liberia and Sierra Leone could reach 1.4 million by January. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Cases to Triple in Weeks Without Drastic Action

WHO: Ebola Cases to Triple in Weeks Without Drastic Action

AFP (Sep. 23, 2014) The number of Ebola infections will triple to 20,000 by November, soaring by thousands every week if efforts to stop the outbreak are not stepped up radically, the WHO warned in a study on Tuesday. Duration: 01:01 Video provided by AFP
Powered by NewsLook.com
5 Ways Men Can Prevent Most Heart Attacks

5 Ways Men Can Prevent Most Heart Attacks

Newsy (Sep. 23, 2014) No surprise here: A recent study says men can reduce their risk of heart attack by maintaining a healthy lifestyle, which includes daily exercise. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins