Featured Research

from universities, journals, and other organizations

Forcing chromosomes into loops may switch off sickle cell disease

Date:
August 14, 2014
Source:
Children's Hospital of Philadelphia
Summary:
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. This approach may lead to a novel treatment for sickle cell disease, they report.

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.

Related Articles


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 a milder form of the disease. “This observation has been a major driver in the field to understand the molecular basis of the mechanisms that control the biological switch, with the ultimate goal to reverse it,” said Blobel.

In previous research, Blobel’s team used bioengineering techniques to adapt zinc-finger proteins to latch onto specific DNA sites far apart on a chromosome. The chromatin loop that results transmits regulatory signals for specific genes.

In their current work, the scientists custom-designed zinc fingers to flip the biological switch in blood-forming cells, reactivating the genes expressing fetal hemoglobin at the expense of the genes expressing adult hemoglobin. The researchers achieved these results in cultured blood cells from adult mice and adult humans.

The next step, said Blobel, is to apply this proof-of-concept technique to preclinical models, by testing the approach in animals genetically engineered to have manifestations of SCD similar to that found in human patients. If this strategy corrects the disease in animals, it may set the stage to move to human trials.

In principle, added Blobel, the forced chromatin looping approach could also be applied to other hemoglobin-related disorders, such as certain forms of thalassemia in which elevated fetal hemoglobin levels might be beneficial.


Story Source:

The above story is based on materials provided by Children's Hospital of Philadelphia. Note: Materials may be edited for content and length.


Journal Reference:

  1. Wulan Deng, JeremyW. Rupon, Ivan Krivega, Laura Breda, Irene Motta, KristenS. Jahn, Andreas Reik, PhilipD. Gregory, Stefano Rivella, Ann Dean, GerdA. Blobel. Reactivation of Developmentally Silenced Globin Genes by Forced Chromatin Looping. Cell, 2014; 158 (4): 849 DOI: 10.1016/j.cell.2014.05.050

Cite This Page:

Children's Hospital of Philadelphia. "Forcing chromosomes into loops may switch off sickle cell disease." ScienceDaily. ScienceDaily, 14 August 2014. <www.sciencedaily.com/releases/2014/08/140814123424.htm>.
Children's Hospital of Philadelphia. (2014, August 14). Forcing chromosomes into loops may switch off sickle cell disease. ScienceDaily. Retrieved January 25, 2015 from www.sciencedaily.com/releases/2014/08/140814123424.htm
Children's Hospital of Philadelphia. "Forcing chromosomes into loops may switch off sickle cell disease." ScienceDaily. www.sciencedaily.com/releases/2014/08/140814123424.htm (accessed January 25, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, January 25, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Mistakes Should Serve a Lesson Says WHO

Ebola Mistakes Should Serve a Lesson Says WHO

AFP (Jan. 25, 2015) The World Health Organization&apos;s chief on Sunday admitted the UN agency had been caught napping on Ebola, saying it should serve a lesson to avoid similar mistakes in future. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
Disneyland Measles Outbreak Spreads To 5 States

Disneyland Measles Outbreak Spreads To 5 States

Newsy (Jan. 24, 2015) Much of the Disneyland measles outbreak is being blamed on the anti-vaccination movement. The CDC encourages just about everyone get immunized. Video provided by Newsy
Powered by NewsLook.com
Growing Measles Outbreak Worries Calif. Parents

Growing Measles Outbreak Worries Calif. Parents

AP (Jan. 23, 2015) Public health officials are rushing to contain a measles outbreak that has sickened 70 people across 6 states and Mexico. The AP&apos;s Raquel Maria Dillon has more. (Jan. 23) Video provided by AP
Powered by NewsLook.com
Smart Wristband to Shock Away Bad Habits

Smart Wristband to Shock Away Bad Habits

Reuters - Innovations Video Online (Jan. 23, 2015) A Boston start-up is developing a wristband they say will help users break bad habits by jolting them with an electric shock. Ben Gruber reports. Video provided by Reuters
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