An integrated, low-cost, sample-to-answer, CRISPR-based diagnostic detects SARS-CoV-2 and variants from unprocessed saliva.

When scientists alter the genome of an organism, we typically reduce its ability to reproduce in the wild. This limitation has prevented researchers from rendering wild insects unable to spread disease, programing pests to ignore our crops, using genetics to precisely remove environmentally damaging invasive species, and much more. Gene drive occurs when a vertically transmitted genetic element reliably spreads through a population over generations despite providing no reproductive advantage to each host organism. Until recently, scientific efforts to take advantage of this natural phenomenon achieved only limited success. The advent of CRISPR genome editing has dramatically accelerated efforts to harness gene drive. Small groups of scientists may now be capable of unilaterally altering entire wild populations, and through them, the shared environment. Determining whether, when, and how to develop gene drive interventions responsibly will be a defining challenge of our time. Here we describe capabilities, safeguards, applications, and opportunities relevant to gene drive technologies.

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. Summary: Local 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.

The prospect of using genetic methods to target vector, parasite, and reservoir species offers tremendous potential benefits to public health, but the use of genome editing to alter the shared environment will require special attention to public perception and community governance in order to benefit the world. Public skepticism combined with the media scrutiny of gene drive systems could easily derail unpopular projects entirely, especially given the potential for trade barriers to be raised against countries that employ self-propagating gene drives. Hence, open and community-guided development of thoughtfully chosen applications is not only the most ethical approach, but also the most likely to overcome the economic, social, and diplomatic barriers. Here we review current and past attempts to alter ecosystems using biological methods, identify key determinants of social acceptance, and chart a stepwise path for developers towards safe and widely supported use.

Methods of altering wild populations are most useful when inherently limited to local geographic areas. Here we describe a novel form of gene drive based on the introduction of multiple copies of an engineered ‘daisy’ sequence into repeated elements of the genome. Each introduced copy encodes guide RNAs that target one or more engineered loci carrying the CRISPR nuclease gene and the desired traits. When organisms encoding a drive system are released into the environment, each generation of mating with wild-type organisms will reduce the average number of the guide RNA elements per ‘daisyfield’ organism by half, serving as a generational clock. The loci encoding the nuclease and payload will exhibit drive only as long as a single copy remains, placing an inherent limit on the extent of spread.