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Science Papers Report on Chromatin Fiber Sequencing, Mutations Linked to Risk of Cardiovascular Events on Osteoporosis Drug, More

A method for stenciling the structure of individual chromatin fibers onto their composite DNA templates with high precision and resolution is reported by a Harvard Medical School team in Science this week. The technique — called Fiber-seq — uses nonspecific DNA N6-adenine methyltransferases and relies on the ability of single-molecule DNA sequencers to discriminate methylated from unmethylated adenine residues based on the DNA polymerase kinetics at that base during sequencing. "Single-molecule long-read sequencing of chromatin stencils enabled nucleotide-resolution readout of the primary architecture of multi-kilobase chromatin fibers," the scientists write. "Fiber-seq has the potential to provide a unifying tool for analyzing the gene regulatory impact of both rare and common regulatory DNA variation, and for resolving extended regulatory alleles."

Combining data from human genetics and clinical trials, a group led by researchers from the University of Oxford shed new light on the link between the osteoporosis treatment romosozumab and the risk of cardiovascular conditions. Romosozumab is a monoclonal antibody designed to inhibit the glycoprotein sclerostin, a negative regulator of bone formation secreted by osteocytes and encoded by the SOST gene. In Phase III testing, the drug was linked to an excess risk of cardiovascular events. To better understand this issue, the scientists conducted a meta-analysis of published and unpublished cardiovascular outcome trial data of romosozumab and looked at whether genetic variants that mimic therapeutic inhibition of sclerostin are associated with higher risk of cardiovascular disease. They determined that romosozumab use results in an excess risk of cardiac disease and found that SOST mutations that mimic the effects of romosozumab are associated with a higher risk of major adverse cardiovascular events such as heart attack.

Carbon nanocarriers that enable the delivery of small interfering RNAs (siRNAs) into plant cells are described in Science Advances this week. Posttranscriptional gene silencing via siRNA-mediated RNA interference is widely used for plant research, but direct siRNA delivery is hampered by the cell wall of plants. As a result, viral vectors are employed for delivery, but these have their own limitations. To address this, University of California, Berkeley scientists developed single-walled carbon nanotubes that can deliver separate single-stranded siRNAs into intact plant cells, where they hybridize and trigger targeted gene silencing. The work, they write, "establishes that nanotubes could enable a myriad of plant biotechnology applications that rely on RNA delivery to intact cells."