Researchers from Penn Medicine and Children’s Hospital of Philadelphia have fixed a lethal mutation in the prenatal mouse models of a rare pulmonary disease. The hope is that the approach of in utero editing described in Science Translational Medicine will work for other congenital lung diseases as well.
I asked one of the corresponding authors, Edward Morrison, scientific director of the Penn’s Institute for Regenerative Medicine, to explain what they have done and what to expect next. See Q&A below. Continue reading
If you know the enemy and know yourself, you need not fear the result of a hundred battles. The military strategist Sun Tzu wrote it over two thousand years ago, but this quote could also apply to oncology research in the CRISPR era. Identifying the weak points of cancer cells is the first step to hit new molecular targets with the next generation of drugs.
The good news is that the Wellcome Sanger Institute has taken a giant leap toward this goal, drawing up a list of 600 candidate genes. The study just published in Nature by Mathew Garnett’s team comes with a twin paper by the Broad Institute, confirming the results by following an alternative approach. In a four-year tour de force of functional genomics, Sanger’s researchers used CRISPR to disrupt every gene in over 300 cancer models from 30 cancer types. From this amount of data, they developed a prioritization system which will guide big pharma’s hunt for new drugs.
Do you remember the alarm about the cancer risks of CRISPR? According to a study published in Cell Stem Cell by Italian researchers, the DNA-damage response is not such a big problem in edited cells. At least not in hematopoietic stem cells edited with highly specific nucleases. Continue reading
In 2013, multiple labs sharpened CRISPR molecular scissors against Duchenne muscular dystrophy, using cells from patients in vitro. In 2016, the dystrophin gene was successfully edited in mice. Then last summer, Eric Olson did it in dogs . Where are we now in the struggle to cure this severe type of myopathy afflicting 300,000 boys in the world? What is still needed to move into a clinical trial? Continue reading
If a donor template is not provided when CRISPR cuts the DNA, broken ends are fixed by natural repairing mechanisms in a way that is considered stochastic and heterogeneous. This makes template-free editing impractical beyond gene disruption, right? Wrong, according to a study published in Nature by Richard Sherwood and colleagues. Continue reading
Healthy adult bimaternal mouse (born to two mothers) with offspring of her own.
Credit: Leyun Wang
Single-gender worlds will remain a sci-fi fantasy. Gay and lesbian couples won’t become parents this way for the foreseeable future. This kind of manipulation is just too risky for humans. But unisexually reproducing mice are an impressive accomplishment, and CRISPR stands out again as a powerful research tool, opening up brand new possibilities for the study of genomic imprinting. For further details, please see the STAT News article about the Cell Stem Cell paper by Zhi-Kun Li.
It’s another CRISPR first: fixing a hereditary disease in utero. Scientists from Pennsylvania University and the Children’s Hospital of Philadelphia used a base editor to rescue tyrosinemia in fetal mice. “The results of this proof-of-concept work demonstrate the possibility of efficiently performing gene editing before birth, pointing to a potential new therapeutic approach for selected congenital disorders,” Avery C. Rossidis and colleagues write in Nature Medicine. Continue reading