Reflection on the Challenges, Accomplishments, and New Frontiers of Gene Drives

Abstract

Ongoing pest and disease outbreaks pose a serious threat to human, crop, and animal lives, emphasizing the need for constant genetic discoveries that could serve as mitigation strategies. Gene drives are genetic engineering approaches discovered decades ago that may allow quick, super-Mendelian dissemination of genetic modifications in wild populations, offering hopes for medicine, agriculture, and ecology in combating diseases. Following its first discovery, several naturally occurring selfish genetic elements were identified and several gene drive mechanisms that could attain relatively high threshold population replacement have been proposed. This review provides a comprehensive overview of the recent advances in gene drive research with a particular emphasis on CRISPR-Cas gene drives, the technology that has revolutionized the process of genome engineering. Herein, we discuss the benefits and caveats of this technology and place it within the context of natural gene drives discovered to date and various synthetic drives engineered. Later, we elaborate on the strategies for designing synthetic drive systems to address resistance issues and prevent them from altering the entire wild populations. Lastly, we highlight the major applications of synthetic CRISPR-based gene drives in different living organisms, including plants, animals, and microorganisms.

A gene drive is a gene drive: the debate over lumping or splitting definitions

“…Researchers studying selfish genetic elements have coined many terms to describe specific phenomena and systems that result in asymmetric inheritance 1 . Many of the original terms describing selfish genetic elements found in nature had mechanistic connotations, including preferential segregation, transmission ratio distortion, meiotic drive, genic meiotic drive, chromosomal meiotic drive, mitotic drive, neocentromere drive, centromere drive, B-chromosome drive, sex-chromosome drive, transposable elements, homing endonucleases, and genetic drive 4 . Today, biotechnology enables researchers to create genetic assemblies in the laboratory that mimic many of these types of natural drives.…”

“…some toxin-antidote systems), and post-meiotic drive systems (e.g. cytoplasmic incompatibility) are currently a major focus of such research and development efforts 4 . The expression “gene drive” has emerged among applied geneticists as a useful generic term to refer to any type of transmission advantage 2 , encompassing a broad array of mechanisms utilized by both natural and synthetic selfish elements 5 , 6 .…”

“…Many synthetic gene drive systems intentionally recapitulate the mechanisms used by naturally occurring selfish elements and thus are functionally the same or similar. For example, the first efforts to create synthetic gene drives using cloning technologies involved repurposing naturally occurring transposable elements and creating chimeric assemblies with drive characteristics similar to the original transposable elements 4 . The synthetic MEDEA gene drive system ( M aternal E ffect D ominant E mbryonic A rrest) simulates some ‘toxin-antidote’-type gene drive systems found widely in nature.…”

Manipulating the plant mycobiome to enhance resilience: Ecological and evolutionary opportunities and challenges

“…In the near future, applications that target chemical signaling to stimulate plant colonization by beneficial fungi or to induce their benefits for the plant may become more widespread [ 5 ]. In the longer term, plant breeding or genetic manipulation to produce varieties that support more beneficial mycobiomes may be an effective strategy [ 6 ], given that historically, breeding has inadvertently shifted plant-fungal associations [ 7 ].…”

Engineered and natural gene drives: mechanistically the same, yet not same in kind

“…In nature, several organisms harbor genes that “selfishly” drive themselves into populations. This natural gene drive uses similar mechanisms to the ones use today to drive engineered genes into laboratory populations 4 . In this article we disagree with James et al 1 who have recently proposed that because natural and engineered gene drives are mechanistically indistinguishable from a molecular standpoint, they should both be referred as “gene drives” because “a gene drive is a gene drive.” We instead propose that two terms be used to distinguish between natural and engineered gene drives, we second Wells and Steinbrecher 5 arguments, and propose to use the terms natural gene drive (NGD) and engineered gene drive (EGD).…”