Targeted Nucleose Technology and knockout rats – guest lecture at NTNU

Yesterday Professor Aron Guerts from the Cardiovascular Research Center and Human Molecular Genetics Center at the Medical College of Wisconsin visited NTNU. Many of us visited his guest lecture, titled “Targeted Nuclease Technology: Empowering genetic engineering beyond the mouse”.

Over the past five to ten years, a suite of revolutionary tools has emerged and created a new field of “Genome Editing”. During the last 20 years, precision modification of a genome was basically restricted to the mouse model and their embryonic stem cells from a couple of common strains. Scientific progressions within the field have now made it possible to engineer precise mutations and genetic modifications to essentially any genome of any cell from any strain or species.

Photo: HeadSpin

Photo: HeadSpin

With the term Targeted Nuclease Technology (TNT), Guerts especially points to the three following discoveries:

  • The Zinc-Finger Nucleases (ZFNs), an artificial restricion enzyme improving the targeting of unique sequences within complex genomes.
  • Transcription activator-like effector nucleases (TALENs) – another restriction enzyme, generated by fusing a TAL effector DNA binding domain to a DNA cleavage domain. This type of enzymes cut DNA strands at a specific secuence. The advantage of transcription activator-like effectors (TALEs) is that they can be engineered to bind practically any desired DNA sequence. This enables genome editing when TALENs are introduced into cells.
  • RNA-Guided Nucleases (RGNs) (CRISPR/Cas9), programmable endonucleases also involved in targeted genome editing. 

These discoveries have vastly expanded the possibilities for both basic research of the genome and for promising therapeutic strategies. Guert’s research group at the Medical College of Wisconsin has explored the use of TNT to laboratory rat and mouse disease model strains to create resources of gene knock-out models, specific gene knock-in strains, and for generating conditional (Cre/loxP-based) knockout models.  When combined with other transgenic tools, they are now empowering rat researchers across the globe to address gene-centered hypotheses in widely studied physiological, pharmacological, biochemical, and behavioral model systems.

Guerts is a key contributor to this exciting technology development and was responsible for the world’s first targeted gene knockout rats. For  a more thorough description, you can read about the Knockout Rats in a Science article from 2009.

Maria Henningsen, CERG