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CRISPR/Cas9-Labeled DNA Imaged with DVD Optics

  • If whole-genome sequencing (WGS) is like clicking through a DVD frame by frame, and if fluorescence in situ hybridization (FISH) is like scanning the scene-selection menu, a new technology may offer an intermediate-viewing option. This new technology, high-speed atomic force microscopy (HS-AFM) nanomapping, can create images of up to a million base pairs in size. Although HS-AFM nanomapping cannot match the single-base-pair resolution of DNA sequencing, it has the virtue of greater speed. It can fast-forward to DNA maps offering a resolution of tens of base pairs.

    Although HS-AFM nanomapping hasn’t appeared in any high-production-value trailers, a coming attraction of sorts became available November 21 in Nature Communications, in an article entitled, “DNA nanomapping using CRISPR/Cas9 as a programmable nanoparticle.” This article, which was submitted by Virginia Commonwealth University scientists, suggests that HS-AFM nanomapping may fill technical gaps that are poorly addressed by existing DNA-mapping techniques.

    The article also explains how HS-AFM nanomapping represents the merger of technical advances in DNA nanotechnology and single-molecule genomics. “We describe a labeling technique (CRISPR/Cas9 nanoparticles) for high-speed AFM-based physical mapping of DNA,” wrote the article’s authors, “and the first successful demonstration of using DVD optics to image DNA molecules with high-speed AFM.”

    The Virginia Commonwealth University scientists, led by physicist Jason Reed, Ph.D., anticipate that their new nanomapping technology could transform the way disease-causing genetic mutations are diagnosed and discovered. To demonstrate the nanomapping technology, Dr. Reed and colleagues mapped the genetic translocations present in lymph node biopsies of lymphoma patients.

    While there are many potential uses for this technology, Dr. Reed and his team expect that they will, in the immediate future, remain focused on medical applications. They are currently developing software based on existing algorithms that can analyze patterns in sections of DNA up to and over a million base pairs in size. Once the software is completed, it may be combined with a shoe-box-sized instrument to give pathology labs another way to diagnose and evaluate the treatment of diseases linked to genetic mutations.

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