Gus R. McFarlane

Bio: Gus R. McFarlane is an academic researcher from University of Edinburgh. The author has contributed to research in topics: Gene drive & Population. The author has an hindex of 4, co-authored 8 publications receiving 64 citations.

On-Farm Livestock Genome Editing Using Cutting Edge Reproductive Technologies

Abstract: The global demand for animal-based food products is anticipated to increase by 70% by 2050. Meeting this demand in a way that has minimal impact on the environment will require the implementation of advanced technologies. Genome editing of livestock is a tool that will allow breeders to improve animal welfare, performance and efficiency, paving the way to a more sustainable future for livestock agriculture. Currently, genome editing of livestock is limited to specialised laboratories due to the complexity of techniques available for the delivery of genome editing reagents into zygotes and reproductive cells. The emergence of three cutting-edge reproductive technologies – (i) zygote electroporation, (ii) zygote transduction of recombinant adeno-associated virus (rAAV), and (iii) surrogate sire technology – will provide livestock breeders with a new toolkit of delivery strategies for genome editing. The simplicity of these technologies will enable widespread on-farm application in major livestock species by seamlessly integrating into current breeding systems. We believe it is timely to highlight these three cutting-edge reproductive technologies for genome editing and have outlined pipelines for their implementation in on-farm settings. With a nuanced regulatory framework these technologies could fast-track livestock genetic gain and help secure a sustainable future for livestock.

Novel combination of CRISPR-based gene drives eliminates resistance and localises spread.

Abstract: Invasive species are among the major driving forces behind biodiversity loss. Gene drive technology may offer a humane, efficient and cost-effective method of control. For safe and effective deployment it is vital that a gene drive is both self-limiting and can overcome evolutionary resistance. We present HD-ClvR in this modelling study, a novel combination of CRISPR-based gene drives that eliminates resistance and localises spread. As a case study, we model HD-ClvR in the grey squirrel (Sciurus carolinensis), which is an invasive pest in the UK and responsible for both biodiversity and economic losses. HD-ClvR combats resistance allele formation by combining a homing gene drive with a cleave-and-rescue gene drive. The inclusion of a self-limiting daisyfield gene drive allows for controllable localisation based on animal supplementation. We use both randomly mating and spatial models to simulate this strategy. Our findings show that HD-ClvR could effectively control a targeted grey squirrel population, with little risk to other populations. HD-ClvR offers an efficient, self-limiting and controllable gene drive for managing invasive pests.

Novel combination of CRISPR-based gene drives eliminates resistance and localises spread

Abstract: Invasive species are among the major driving forces behind biodiversity loss. Gene drive technology may offer a humane, efficient and cost-effective method of control. For safe and effective deployment it is vital that a gene drive is both self-limiting and can overcome evolutionary resistance. We present HD-ClvR, a novel combination of CRISPR-based gene drives that eliminates resistance and localises spread. As a case study, we model HD-ClvR in the grey squirrel (Sciurus carolinensis), which is an invasive pest in the UK and responsible for both biodiversity and economic losses. HD-ClvR combats resistance allele formation by combining a homing gene drive with a cleave-and-rescue gene drive. The inclusion of a self-limiting daisyfield gene drive allows for controllable localisation based on animal supplementation. We use both randomly mating and spatial models to simulate this strategy. Our findings show that HD-ClvR can effectively control a targeted grey squirrel population, with little risk to other populations. HD-ClvR offers an efficient, self-limiting and controllable gene drive for managing invasive pests.

Livestock breeding for the 21st century: the promise of the editing revolution

Abstract: In recent years there has been a veritable explosion in the use of genome editors to create sitespecific changes, both in vitro and in vivo, to the genomes of a multitude of species for both basic research and biotechnology. Livestock, which form a vital component of most societies, are no exception. While selective breeding has been hugely successful at enhancing some production traits, the rate of progress is often slow and is limited to variants that exist within the breeding population. Genome editing provides the potential to move traits between breeds, in a single generation, with no impact on existing productivity or to develop de novo phenotypes that tackle intractable issues such as disease. As such, genome editors provide huge potential for ongoing livestock development programs in light of increased demand and disease challenge. This review will highlight some of the more notable agricultural applications of this technology in livestock.

The potential of genomics for restoring ecosystems and biodiversity.

Abstract: Billions of hectares of natural ecosystems have been degraded through human actions. The global community has agreed on targets to halt and reverse these declines, and the restoration sector faces the important but arduous task of implementing programmes to meet these objectives. Existing and emerging genomics tools offer the potential to improve the odds of achieving these targets. These tools include population genomics that can improve seed sourcing, meta-omics that can improve assessment and monitoring of restoration outcomes, and genome editing that can generate novel genotypes for restoring challenging environments. We identify barriers to adopting these tools in a restoration context and emphasize that regulatory and ethical frameworks are required to guide their use.

Population management using gene drive: molecular design, models of spread dynamics and assessment of ecological risks

Abstract: CRISPR gene drive has recently been proposed as a promising technology for population management, including in conservation genetics. The technique would consist in releasing genetically engineered individuals that are designed to rapidly propagate a desired mutation or transgene into wild populations. Potential applications in conservation biology include the control of invasive pest populations that threaten biodiversity (eradication and suppression drives), or the introduction of beneficial mutations in endangered populations (rescue drives). The propagation of a gene drive is affected by different factors that depend on the drive construct (e.g. its fitness effect and timing of expression) or on the target species (e.g. its mating system and population structure). We review potential applications of the different types of gene drives for conservation. We examine the challenges posed by the evolution of resistance to gene drives and review the various molecular and environmental risks associated with gene drives (e.g. propagation to non target populations or species and unintended detrimental ecosystem impacts). We provide some guidelines for future gene drive research and discuss ethical, biosafety and regulation issues

Genetic Biocontrol for Invasive Species

Abstract: Invasive species are increasingly affecting agriculture, food, fisheries, and forestry resources throughout the world. As a result of global trade, invasive species are often introduced into new environments where they become established and cause harm to human health, agriculture, and the environment. Prevention of new introductions is a high priority for addressing the harm caused by invasive species, but unfortunately efforts to prevent new introductions do not address the economic harm that is presently manifested where invasive species have already become established. Genetic biocontrol can be defined as the release of organisms with genetic methods designed to disrupt the reproduction of invasive populations. While these methods offer the potential to control or even eradicate invasive species, there is a need to ensure that genetic biocontrol methods can be deployed in a way that minimizes potential harm to the environment. This review provides an overview of the state of genetic biocontrol, focusing on several approaches that were the subject of presentations at the Genetic Biocontrol for Invasive Species Workshop in Tarragona, Spain, March 31st, 2019, a workshop sponsored by the OECD's Co-operative Research Program on Biological Resource Management for Sustainable Agricultural Systems. The review considers four different approaches to genetic biocontrol for invasive species; sterile-release, YY Males, Trojan Female Technique, and gene drive. The different approaches will be compared with respect to the efficiency each affords as a genetic biocontrol tool, the practical utility and cost/benefits associated with implementation of the approach, and the regulatory considerations that will need to be addressed for each. The opinions expressed and arguments employed in this publication are the sole responsibility of the authors and do not necessarily reflect those of the OECD or of the governments of its Member countries.

A transcomplementing gene drive provides a flexible platform for laboratory investigation and potential field deployment.

Abstract: CRISPR-based gene drives can spread through wild populations by biasing their own transmission above the 50% value predicted by Mendelian inheritance. These technologies offer population-engineering solutions for combating vector-borne diseases, managing crop pests, and supporting ecosystem conservation efforts. Current technologies raise safety concerns for unintended gene propagation. Herein, we address such concerns by splitting the drive components, Cas9 and gRNAs, into separate alleles to form a trans-complementing split–gene-drive (tGD) and demonstrate its ability to promote super-Mendelian inheritance of the separate transgenes. This dual-component configuration allows for combinatorial transgene optimization and increases safety by restricting escape concerns to experimentation windows. We employ the tGD and a small–molecule-controlled version to investigate the biology of component inheritance and resistant allele formation, and to study the effects of maternal inheritance and impaired homology on efficiency. Lastly, mathematical modeling of tGD spread within populations reveals potential advantages for improving current gene-drive technologies for field population modification. Gene drives raise safety concerns around unintended propagation. Here the authors present a trans-complementing split-gene drive that requires inheritance of separate transgenes to assemble a fully functional drive.

Prevention not cure: a review of methods to avoid sea lice infestations in salmon aquaculture

Abstract: The Atlantic salmon aquaculture industry still struggles with ectoparasitic sea lice despite decades of research and development invested into louse removal methods In contrast, methods to prevent infestations before they occur have received relatively little research effort, yet may offer key benefits over treatment‐focused methods Here, we summarise the range of potential and existing preventative methods, conduct a meta‐analysis of studies trialling the efficacy of existing preventative methods and discuss the rationale for a shift to the prevention‐focused louse management paradigm Barrier technologies that minimise host–parasite encounter rates provide the greatest protection against lice, with a weighted median 76% reduction in infestation density in cages with plankton mesh ‘snorkels’ or ‘skirts’, and up to a 100% reduction for fully enclosed cages Other methods such as geographic spatiotemporal management, manipulation of swimming depth, functional feeds, repellents and host cue masking can drive smaller reductions that may be additive when used in combination with barrier technologies Finally, ongoing development of louse‐resistant salmon lineages may lead to long‐term improvements if genetic gain is maintained, while the development of an effective vaccine remains a key target Preventative methods emphasise host resistance traits while simultaneously reducing host–parasite encounters Effective implementation has the potential to dramatically reduce the need for delousing and thus improve fish welfare, productivity and sustainability in louse‐prone salmon farming regions