Daisyfield gene drive systems harness repeated genomic elements as a generational clock to limit spread

Min, Jie; Noble, Charleston; Najjar, Devora; Esvelt, Kevin M.

doi:10.1101/104877

Cited by 26 publications

(30 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A proposed further iteration of the daisy drive is the daisyfield drive . In contrast to the daisy drive, where a linear chain of components is required for drive (for instance, C drives B drives A), the daisyfield drive uses many copies of a single non‐driving component B to induce propagation of a drive cassette (component A) through a population (Fig.…”

Section: Safeguarding Crispr Drivesmentioning

confidence: 99%

The promise and peril of CRISPR gene drives

Zentner

Wade

2017

BioEssays

View full text Add to dashboard Cite

Gene drives are selfish genetic elements that use a variety of mechanisms to ensure they are transmitted to subsequent generations at greater than expected frequencies. Synthetic gene drives based on the clustered regularly interspersed palindromic repeats (CRISPR) genome editing system have been proposed as a way to alter the genetic characteristics of natural populations of organisms relevant to the goals of public health, conservation, and agriculture. Here, we review the principles and potential applications of CRISPR drives, as well as means proposed to prevent their uncontrolled spread. We also focus on recent work suggesting that factors such as natural genetic variation and inbreeding may represent substantial impediments to the propagation of CRISPR drives.

show abstract

Section: Safeguarding Crispr Drivesmentioning

confidence: 99%

The promise and peril of CRISPR gene drives

Zentner

Wade

2017

BioEssays

View full text Add to dashboard Cite

show abstract

“…of complex constructs such as those that carry multiple anti-pathogen effectors or those designed around the use of multi-gRNA arrays have all to satisfy regulatory requirements. Along the same lines, limiting the propagation of gene drives by inserting them into repetitive genomic regions while attractive in principle presents a formidable genome engineering challenge (Min et al 2017) .…”

Section: Introductionmentioning

confidence: 99%

Integral Gene Drives: an “operating system” for population replacement

Nash

Urdaneta

Beaghton

et al. 2018

Preprint

View full text Add to dashboard Cite

First generation CRISPR-based gene drives have now been tested in the laboratory in a number of organisms including malaria vector mosquitoes. A number of challenges for their use in the area-wide genetic control of vector-borne disease have been identified. These include the development of target site resistance, their long-term efficacy in the field, their molecular complexity, and the practical and legal limitations for field testing of both gene drive and coupled anti-pathogen traits. To address these challenges, we have evaluated the concept of Integral Gene Drive (IGD) as an alternative paradigm for population replacement. IGDs incorporate a minimal set of molecular components, including both the drive and the anti-pathogen effector elements directly embedded within endogenous genes -an arrangement which we refer to as gene "hijacking". This design would allow autonomous and non-autonomous IGD traits and strains to be generated, tested, optimized, regulated and imported independently. We performed quantitative modelling comparing IGDs with classical replacement drives and show that selection for the function of the hijacked host gene can significantly reduce the establishment of resistant alleles in the population while hedging drive over multiple genomic loci prolongs the duration of transmission blockage in the face of pre-existing target-site variation. IGD thus has the potential to yield more durable and flexible population replacement traits.

show abstract

“…Daisy-chain drive systems comprise a linked series of elements in which each drives the next in the chain; because the daisy element at the base of the chain does not drive, it is lost in half of offspring, successively depriving subsequent elements of their inheritance advantage 9 . In daisyfield drive systems, many daisy elements all target the same allele and cause it to drive; their number decreases by half with every generation of mating with wild-type organisms until none are left and drive ceases 10 .…”

Section: Introductionmentioning

confidence: 99%

Daisy quorum drives for the genetic restoration of wild populations

Min

Noble

Najjar

et al. 2017

Preprint

Self Cite

View full text Add to dashboard Cite

An ideal gene drive system to alter wild populations would 1) exclusively affect organisms within the political boundaries of consenting communities, and 2) be capable of restoring any engineered population to its original genetic state. Here we describe ‘daisy quorum’ drive systems that meet these criteria by combining daisy drive with underdominance. A daisy quorum drive system is predicted to spread through a population until all of its daisy elements have been lost, at which point its fitness becomes frequency-dependent: mostly altered populations become fixed for the desired change, while engineered genes at low frequency are swiftly eliminated by natural selection. The result is an engineered population surrounded by wild-type organisms with limited mixing at the boundary. Releasing large numbers of wild-type organisms or a few bearing a population suppression element can reduce the engineered population below the quorum, triggering elimination of all engineered sequences. In principle, the technology can restore any drive-amenable population carrying engineered genes to wild-type genetics. Daisy quorum systems may enable efficient, community-supported, and genetically reversible ecological engineering.SummaryLocal communities should be able to control their own environments without forcing those choices on others. Ideally, each community could reversibly alter local wild organisms in ways that cannot spread beyond their own boundaries, and any engineered population could be restored to its original genetic state. We've invented a 'daisy quorum' drive system that appears to meet these criteria.“Daisy” refers to a daisy drive, which typically uses a daisy-chain of linked genes to spread a change through a local population while losing links every generation until it stops spreading. “Quorum” reflects the system's ability to “vote” on whether a local population should be altered or not: once all daisy elements are lost, it favors replication by the altered version or the original depending on which is more abundant in the local area. Put together, they result in a change that first spreads through a local population, then either becomes locally prevalent is eliminating, inhibiting mixing at the boundary. All organisms in the target population are altered, but changes are unable to spread much beyond that area due to being greatly outnumbered by wild-type organisms and consequently less able to replicate.We haven't yet performed any experiments involving daisy quorum systems. Rather, we’re describing what we intend to do, including the safeguards we will use and our assessment of risks, in the hope that others will evaluate our plans and tell us if there's anything wrong that we missed. We hope that all researchers working on gene drive systems - and other technologies that could impact the shared environment - will similarly pre-register their plans. Sharing plans can reduce needless duplication, accelerate progress, and make the proposed work safer for everyone.

show abstract

Daisyfield gene drive systems harness repeated genomic elements as a generational clock to limit spread

Cited by 26 publications

References 21 publications

The promise and peril of CRISPR gene drives

The promise and peril of CRISPR gene drives

Integral Gene Drives: an “operating system” for population replacement

Daisy quorum drives for the genetic restoration of wild populations

Contact Info

Product

Resources

About