CRISPR technology moving toward human gene therapy

Researchers at the University of Pennsylvania are reporting they have used a CRISPR/Cas9-mediated gene targeting system to “cure” hemophilia B, caused by mutations in the blood clotting factor IX gene, in mice. Their research, presented at the American Society of Hematology annual meeting in December 2016, included data collected over four months posttreatment. The proof-of-concept research demonstrates the potential of the new approach to gene therapy but still relies on adeno-associated viral vectors, which come with their own risks, to deliver the functional components. Lili Wang, research associate professor in the Penn Gene Therapy Program (GTP), and James M Wilson, professor of medicine and GTP director, led the research. The method specifically targets a region of the mouse factor IX gene and contains a partial human factor IX complementary DNA sequence. The researchers say the vector could potentially be used in patients with any mutations in the factor IX gene: The announcement comes as Penn researchers are poised to begin the first human clinical trials in the United States to use CRISPR gene-editing technology. A Penn-led team will be manufacturing T cells edited to treat cancer patients in a trial funded by the new Parker Institute for Cancer Immunotherapy. This phase I safety trial of 18 patients with several types of cancer will attempt to target cancer cells for immune system destruction. —Karyn Hede, News Editor

Ancient tree duplicated genes to survive, outlasting dinosaurs

Fossil hunters cracking open rocks that harbor leafy remains of ancient seabeds would be hard-pressed to distinguish fossilized ginkgo leaves from those of their living relatives, now dispersed globally. The ancient tree, which lived alongside dinosaurs during the Jurassic period, has changed little since then. Recently, the hardy survivor’s genome was finally sequenced, revealing secrets behind the evolution of seed plants. Wenbin Chen from the Beijing Genomics Institute led the tedious effort to complete the enormous 10.61 GB genome (three times as large as the genome of us humans!) with its 41,840 annotated genes and many repeated sequences, including long terminal repeat retrotransposons, which are unusually prevalent. The researchers concluded that the whole genome may have been duplicated at some point, possibly twice. The newly completed genome, published November 2016 in the journal GigaScience, will assist in the assembly and annotation of the published genome drafts of pines and other gymnosperms. In addition, the research team focused on evidence of expansion of gene families that provide defense against pests and disease. Widely known for its longevity and hardiness, the gingko survived periods of glaciation in China that killed many other species as well as, of course, the extreme environmental upheavals that finished off the dinosaurs. The ginkgo’s arsenal of weapons includes synthesis of chemicals that directly fight insect damage and indirectly target insects by attracting enemies of plant-eating insects. These findings indicate that having multiple genetic strategies, including expansion of gene families, higher doses of specific genes, and a variety of defensive genes, might contribute to the tree’s longevity and resilience. —Karyn Hede, News Editor