Clean correction of a patient’s genetic mutation

For the first time, scientists have cleanly corrected a human gene mutation in a patient’s stem cells. The result, reported in Nature last week, brings the possibility of personalised cell therapy for genetic disorders of the liver closer to becoming a reality.

The team, led by researchers from the Wellcome Trust Sanger Institute and the University of Cambridge, targeted a gene mutation responsible for both cirrhotic liver disease and lung emphysema. Using cutting-edge methods, they were able to correct the sequence of a patient’s genome, remove all exogenous DNA and show that the corrected gene worked normally.

Building on previous work from Cambridge which showed that it was possible to transform skin cells into liver cells by reprogramming stem cells, the team successfully and accurately corrected a mutation in a gene causing alpha1-antitrypsin deficiency. Using ‘molecular scissors’ to snip the genome at precisely the right place, they then inserted a correct version of the gene using a DNA transporter called piggyBac. The piggyBac sequences were subsequently removed from the cells, allowing them to be converted into liver cells without any trace of residual DNA damage at the site of correction. The corrected cells were then shown to be producing normal alpha1-antitrypsin protein.

Dr Ludovic Vallier, Medical Research Council senior Fellow and Principal Investigator at the University of Cambridge’s MRC Centre for Stem Cell Biology and Regenerative Medicine said “We still have major challenges to overcome before any clinical applications but we have now the tools necessary to advance toward this essential objective.”

For the full article from University of Cambridge Research News click here

Yusa K, Rashid ST, Strick-Marchand H, Varela I, Liu PQ, Paschon DE, Miranda E, Ordóñez A, Hannan NR, Rouhani FJ, Darche S, Alexander G, Marciniak SJ, Fusaki N, Hasegawa M, Holmes MC, Di Santo JP, Lomas DA, Bradley A, Vallier L: “Targeted gene correction of α(1)-antitrypsin deficiency in induced pluripotent stem cells.”  Nature. 2011 Oct 12. doi:10.1038/nature10424 link


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Scientists demonstrate potential new treatment for most common form of infant leukaemia

Cambridge scientists based at the Wellcome Trust/Cancer Research UK Gurdon Institute and the Cambridge Institute for Medical Research at the University of Cambridge have shown that a potential new drug could treat mixed-lineage leukaemia (MLL) according to a study published in Nature on the 2nd October.

The researchers showed that a chemical agent called I-BET151 mimics certain chemical tags and prevents the BET family of proteins and a gene called MLL from fusing with and activating leukaemia genes. Treatment of leukaemias in mice and human cancer cells in the lab showed that the chemical could halt the disease, paving the way for its use in patient trials.

Dr Brian Huntly, who co-led the study and is based at the Cambridge Institute for Medical Research at the University of Cambridge, said: “MLL leukaemia is very hard to treat and often the only option for patients who have become resistant to standard treatments is a bone marrow transplant. We hope these findings may in future mean that fewer children need this procedure.”

To read the full article from University of Cambridge research news click here

Dawson MA, Prinjha RK, Dittman A, Giotopoulos G, Bantscheff M, Chan W-i, Robson SC, Chung C-w, Hopf C, Savitski MM, Huthmacher C, Gudgin E, Lugo D, Beinke S, Chapman TD, Roberts EJ, Soden PE, Auger KR, Mirguet O, Doehner K, Delwel R, Burnett AK, Jeffrey P, Drewes G, Lee K, Huntly BJP, Kouzarides T “Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia” Nature (2011) doi:10.1038/nature10509 link


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Scientists create mammalian cells with single chromosome set

Researchers at the University of Cambridge have for the first time created mammalian stem cells containing a single set of chromosomes from an unfertilised Mouse egg in research published in Nature last week.

The technique has previously been used in Zebrafish but this is the first time it has been used to generate mammalian stem cells. The technique should allow scientists to better establish the relationships between genes and their function.

Dr Anton Wutz of the Wellcome Trust said “Any genetic change we introduce to the single set of chromosomes will have an easy-to-determine effect. This will be useful for exploring in a systematic way the signalling mechanisms within cell and how networks of genes regulate development.”

To read the full story from University of Cambridge Research News click here

Leeb M, Wutz A, “Derivation of haploid embryonic stem cells from mouse embryos.” Nature 2011 Sep 7. doi: 10.1038/nature10448 Link


Image by Anton Wutz

Gene responsible for regulating chronic pain identified

A gene responsible for regulating chronic pain, called HCN2, has been identified by scientists at the University of Cambridge. The research, published last week in the journal Science, opens up the possibility of targeting drugs to block the protein produced by the gene in order to combat chronic pain.

Following on from promising results in cell cultures, researchers found that mice genetically altered to remove the HCN2 gene did not suffer from neuropathic pain but that their response to acute pain was unaffected.

Professor Peter McNaughton, lead author of the study and Head of the Department of Pharmacology at the University of Cambridge, said: “What is exciting about the work on the HCN2 gene is that removing it – or blocking it pharmacologically- eliminates neuropathic pain without affecting normal acute pain. This finding could be very valuable clinically because normal pain sensation is essential for avoiding accidental damage.”

To read the full article from University of Cambridge Research News click here

Emery EC, Young GT, Berrocoso EM, Chen L, McNaughton PA “HCN2 Ion channels Play a Central Role in Inflammatory and Neuropathic Pain” Science. 2011 Sep 9;333(6048):1462-6 DOI: 10.1126/science.1206243 Link


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Scientists discover how antibiotic molecule found in bacteria stops breast cancer


New research by scientists at the University of Cambridge and published in Nature Chemistry this week has shed light on how thiostrepton ‘clamps’ a cancer-causing protein called FOXM1, preventing it from attaching  to specific stretches of DNA and activating genes that regulate the growth and division of cells.

Lead author, Professor Shankar Balasubramanian said: “This naturally-occurring molecule doesn’t have all the right properties to be used as a breast cancer treatment itself. But this exciting discovery paves the way for the design of more potent and selective drugs based on the structure of thiostrepton to block the FOXM1 protein.”

To read the full article from University of Cambridge research news click here

Nagaratna S. Hegde, Deborah A. Sanders, Raphaël Rodriguez, Shankar Balasubramanian; “The transcription factor FOXM1 is a cellular target of the natural product thiostrepton”  Nature Chemistry Vol 3, P725–731 (2011)  doi:10.1038/nchem.1114 Link


Image by Annie Cavanagh of Wellcome Images


29 new genetic variants associated with MS identified

Scientists have identified 29 new genetic variants linked to multiple sclerosis as well as confirming 23 already known susceptibility loci, providing key insights into the biology of this debilitating neurological disease. The research, involving an international team of investigators led by the Universities of Cambridge and Oxford and funded by the Wellcome Trust, was published on 11 August in the journal Nature

To read the full article from University of Cambridge Research News click here

Sawcer S, Hellenthal G, Pirinen M, Spencer CCA, Donnelly P, Compston S (2011) “Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis”  Nature 476, 214-219 doi:10.1038/nature10251 Link


Image by Benetict Campbell of Wellcome Images

Research sheds light on cell mechanism which plays a role in such diseases as Huntington’s and Parkinson’s

New research from scientists at the University of Cambridge, including Professor David Rubinsztein, provides critical insight into the formation of autophagosomes, which are responsible for cleaning up cellular waste.

To read the full article from University of Cambridge Research News click here

Moreau K, Ravikumar B, Renna M, Puri C, Rubinsztein DC. (2011) “Autophagosome precursor maturation requires homotypic fusion.” Cell 2011 Jul 22;146(2):303-17 doi:10.1016/j.cell.2011.06.023 Link


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