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Genome Editing and Gene Therapies: Complex and Expensive Drugs
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
The main different gene editing methods with the exception of meganucleases (homing endonuclease (LHE) family; for a review, see Stoddard, 2011; 2014) together with their potential they have in drug discovery and the treatment of diseases including personalized therapeutic transplants will be discussed briefly in this chapter with a focus on the CRISPR-Cas system.
The potential for the use of gene drives for pest control in New Zealand: a perspective
Published in Journal of the Royal Society of New Zealand, 2018
Peter K. Dearden, Neil J. Gemmell, Ocean R. Mercier, Philip J. Lester, Maxwell J. Scott, Richard D. Newcomb, Thomas R. Buckley, Jeanne M. E. Jacobs, Stephen G. Goldson, David R. Penman
Building on previous ideas (Craig et al. 1960), Burt (2003) described how gene drive systems based on a homing endonuclease gene (HEG) could be a means for population suppression of pests (Burt 2003; Gould 2008). HEGs are enzymes that cut both strands of a DNA helix at a specific sequence (Belfort & Bonocora 2014). Organisms try to repair such cuts by homology-directed DNA repair (HDR), a process whereby an organism with a double-stranded break in its DNA will try and repair that break by copying any similar sequence it can find in the cell (Jasin & Rothstein 2013). To cause a homing event in a heterozygote, the HEG is inserted into one allele of the site that the HEG actually cuts. When the HEG cuts an empty site, HDR leads to the allele containing the HEG being copied into the cut site. Thus, a heterozygote for the HEG is converted to a homozygote (Figure 1). It is this ‘homing’ property that leads to non-Mendelian inheritance of the HEG and is the basis for the gene drive mechanism (Burt 2003). Modelling has shown that population suppression is particularly efficient if the HEG is targeted to a gene essential for females but not males, or a gene required for reproduction in one sex (Burt 2003; Deredec et al. 2008).
Gene drive to reduce malaria transmission in sub-Saharan Africa
Published in Journal of Responsible Innovation, 2018
Austin Burt, Mamadou Coulibaly, Andrea Crisanti, Abdoulaye Diabate, Jonathan K. Kayondo
First discovered in yeast (Dujon 1989), the homing reaction is a particularly simple mechanism of achieving drive based on the activity of enzymes (‘endonucleases’) that cut specific sequences of DNA (Figure 4). Many microbes have homing endonuclease genes, that spread in populations not because they are useful to the microbe, but because of the gene drive produced by the homing reaction. In animals a synthetic version of the homing reaction was first demonstrated in Drosophila melanogaster (Chan et al. 2011, 2013) and in A. gambiae (Windbichler et al. 2011) using a homing endonuclease (and its recognition site) from yeast. Homing against introduced sequences has also been shown in Drosophila using zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs; Simoni et al. 2014). More recently, high rates of homing have been demonstrated using an RNA-guided Cas9 nuclease against a body colour gene in Drosophila (Gantz and Bier 2015), an eye colour gene in A. stephensi (an Indian vector of malaria; Gantz et al. 2015), and three endogenous female fertility genes in A. gambiae (Hammond et al. 2016).
Identifying and detecting potentially adverse ecological outcomes associated with the release of gene-drive modified organisms
Published in Journal of Responsible Innovation, 2018
Keith R. Hayes, Geoffrey R. Hosack, Genya V. Dana, Scott D. Foster, Jessica H. Ford, Ron Thresher, Adrien Ickowicz, David Peel, Mark Tizard, Paul De Barro, Tanja Strive, Jeffrey M. Dambacher
Gene drive is a generic term for a variety of processes that in sexually reproducing organisms cause genes to be transmitted to successive generations at ratios greater than the classical Mendelian ratio (Champer, Buchman, and Akbari 2016). Natural gene drive processes, such as under dominance and Homing Endonuclease Genes (HEGs), have been known for many decades (Zimmering, Sandler, and Nicoletti 1970), and identified as mechanisms to suppress or modify populations of disease vectors (Wood and Newton 1991; Braig and Yan 2002; Burt 2003; Gould, Magori, and Huang 2006; Lindholm et al. 2016). Harnessing natural drive mechanisms to achieve vector control, however, has proven to be difficult (Smidler, Min, and Esvelt 2017), but this situation could change due to the development of RNA-guided endonucleases such as CRISPR/Cas9 (Jinek et al. 2012).