Gene Drive and Genetic Biocontrol Timeline
The first observations of the skewed inheritance patterns that are characteristic of what we now refer to as ‘gene drive’ were made by a Russian researcher. The year was 1928 and he was studying a species of Drosophila – a fruitfly. The first half of the 20th century saw the discovery of ‘jumping genes’. These are now referred to as transposable elements. They are a common, abundant and very diverse group of ‘gene drives’. They achieve ‘drive’ by creating copies of themselves and inserting them randomly into chromosomes. In the late 1950’s a type of ‘gene drive’ known as ‘meiotic drive’ was discovered. Scientists quickly realized that ‘meiotic drive’ might be used to control insect pests. While notable and important research in the early 21st century is frequently cited as foundational to the history of ‘gene drive’, the timeline presented here illustrates that important ideas originated long before. Only in the 21st century have the technical capabilities been available to readily create ‘gene drives’ in the laboratory.
Contemporary genetic biocontrol research and development, including gene drive, is a culmination of work beginning in the early 20th century. This collection of knowledge from the Virtual Institute’s knowledgebase highlights notable research in the history of genetic biocontrol technology, showing the depth and breadth this ‘field’ of genetics.
Note that ideas emerge in science before they appear in publications. This timeline is intended only to reflect ‘first to publish.’
1900-1950
Early Observations
Barbara McClintock
(1902 – 1992)
Discovered transposable elements, a class of selfish genetic element1950-1975
Basic Genetics & Applications
Edward F. Knipling
(1909 – 2000)
Explored genetic control of insect vectors of human pathogens and parasites1975-2000
Molecular Genetic & Transgenic Technologies
Christopher Curtis
(1939 – 2008)
Explored genetic control of insect vectors of human pathogens and parasites2000-today
Gene Editing Technologies
Austin Burt
First proposed the use of homing endonucleases as gene drive platforms.
1900 - 1950
Early ObservationsBarbara McClintock (1902 – 1992)
Discovered transposable elements, a class of selfish genetic elementThe earliest reports of skewed patterns of inheritance which today we would refer to as ‘drive’ were made in the first half of the 20th century, although the term ‘drive’ was not used until 1957. This period also saw the earliest ideas and experiments involving genetic biocontrol.
Gershenson (1928) made a very early observation of ‘drive’ while studying Drosophila fruitflies.
Serebrovskii (1940) describes how chromosome translocations and the resulting sterility translocation heterozygotes could be the basis for controlling insect populations, the earliest articulation of the idea of genetic biocontrol.
Rhoades (1942) made the first recorded observation of ‘meiotic drive’ in plants while studying maize.
Östergren (1945) was the first to refer to the behavior of ‘B chromosomes’ as parasitic, a concept that preceded ‘selfish genetic elements’.
Potts (1944) and Vanderplank (1944) describe the idea of using hybrid incompatability as a insect control tool independently of Serebrovskii (1940).
Vanderplank (1947) reports extensive hybridization experiments among tsetse species and an attempt to remove a species through the use of hybrid incompatability in the field, one of the earliest attempts of genetic biocontrol.
McClintock (1948) reports the ‘transposition’ of Ac/Ds in maize, a transposable element system. This is a seminal paper not only in the history of the study of selfish genetic elements but in the history of genetics.
Citations
A new sex-ratio abnormality in Drosophila obscura
S. Gershenson, Genetics, 13:488. 1928.
1. The sex-ratio in the normal lines of Drosophila obscura is very near to the theoretical 1 : 1. 2. Out of 19 females caught in nature, two were heterozygous for a gene which causes strong deviations in the normal sex distribution. 3. The researches made have shown that this ...
On the possibility of a new method for the control of insect pests.
A. S. Serebrovskii, Zoologicheskiĭ zhurnal, 19:618-630 (in Russian). 1940.
ON THE POSSIBILITY OF A NEW METHOD FOR THE CONTROL OF INSECT PESTS. The new principle of insect control consists in disturbing the propagation of the pest population by means of translocations. It is well known that individuals heterozygous for some translocations usually form a ...
Preferential segregation in maize
M. M. Rhoades, Genetics, 27:395-407. 1942.
An abnormal type of chromosome 10, found by Longley in maize from the s.-w. part of the U. S., is preferentially segregated during megasporogenesis. More than 70% of the ovules receive the abnormal chromosome instead of the 50% expected with random segregation. At pachytene the ...
Hybridization between Glossina Species and Suggested New Method for Control of Certain Species of Tsetse
F. L. Vanderplank, Nature, 154:607-608. 1944.
Corson and Potts record crossing Glossina swynnertoni Aust. with G. morsitans Westwood. Corson crossed twelve female G. morsitans with male G. swynnertoni, of which only two females produced a total of three pupæ. All his females lived long enough for reproduction to take place. ...
Tsetse hybrids
W. H. Potts, Nature, 154:606-607. 1944.
IN 1936 I attempted to cross various species of tsetse (Glossina) with the idea that, should they hybridize readily, and should the resultant hybrids prove sterile, this might be tried as a measure of control. Corson had already, in 1932, obtained three offspring from crosses ...
Parasitic nature of extra fragment chromosomes
Östergren G., Botaniska Notiser, 2:157-163. 1945.
This paper is intended as a contribution to the discussion concerning the significance of the extra fragments or »accessory chromosomes» as they are called by Håk ansso n(1945), which are not too rarely found in cross-fertilizing populations. I think reasonable support may ...
Experiments in the hybridisation of tsetse-flies (Glossina, Diptera) and the possibility of a new method of control.
F. L. Vanderplank, Transactions of the Royal Entomological Society of London, 98:1-18. 1947.
Hybridisation of Glossina morsitans Westwood, G. swynnertoni Austen and G. pallidipes Austen was attempted in order to discover(a) Whether the three could be regarded as distinct species or as sub-species of morsitans ; (b) Whether they would mate freely with one another, and if ...
Mutable loci in maize.
B. McClintock, Carnegie Inst. Washington Year Book, 47:155-169. 1948.
Previous reports have state that the number of unstable loci have recently arisen in maize culture. In a particular cell of a plant, a normal "wild-type" locus becomes altered; the normal, dominant expression of this locus changes and gives rise to a recessive expression (or, in ...1950 - 1975
Basic Genetics & ApplicationsEdward F. Knipling ( 1909 – 2000)
Explored genetic control of insect vectors of human pathogens and parasitesThis period of 25 years saw the development of solid foundations in the study of selfish genetic elements (gene drive), the first successful application of genetic biocontrol to control an insect and the birth of the idea of ‘population replacement’ as a malaria control measure.
Knipling (1955) was the first peer-reviewed publication in which the inventor of the first genetic biocontrol technology, the sterile insect technique, describes the concepts and genetics.
Baumhover et al. (1955) report the successful application of the sterile insect technique to a significant livestock pest on the island of Curaçao.
Sandler and Novitski (1957) review genetic phenomenon of skewed inheritance and coin the terms ‘meiotic drive’, ‘chromosomal meiotic drive’ and ‘genic meiotic drive’; the first use of the term ‘drive’ in relation to transmission ratio distorting genetic systems.
Dunn (1957) describes the distorted transmission of the tailless locus in mice, one of the earliest descriptions of ‘drive’ in mammals.
Cameron and Moav (1957) describe a ‘meiotic drive’ system in tobacco that they refer to as pollen killer, a heretofore unique mechanism of achieving ‘drive’.
Jones (1957) proposes the replacement of malaria susceptible mosquitoes with refractory strains as a way to control malaria. This is an early expression of the idea of population replacement that continues to motivate vector control research and development.
Sandler et al. (1959) describe a newly discovered locus in the fruitfly, Drosophila melanogaster, displaying ‘meiotic drive’ called Segregation Distorter (SD). SD went on to be a continuous source of great insights into selfish genetic elements and ‘gene drive’.
Craig et al. (1960) describe a sex-ratio distorting genetic ‘factor’ in the yellow fever mosquito, Aedes aegypti, that results in a preponderance of males and how it could be the basis for genetics-based mosquito control strategies.
Von Borstel and Buzzati-Traverso (1962) are the first to recognize and propose that ‘meiotic drive’ might form the basis for controlling economically important and undesirable populations of insects. This is the published report of a paper presented at a meeting in 1960.
Hamilton (1967) publishes his comprehensive consideration of the biology and evolutionary implications of sex-chromosome drives and includes a discussion of the potential use of these selfish genetic elements as the basis for controlling harmful pest populations.
Lavan (1967) reports on the local eradication of Culex pipiens fatigans in Burma using cytoplasmic incompatibility.
Curtis (1968) describes how translocations could be used to drive and fix desirable genes into pest insect populations.
Childress (1972) reports laboratory population cage data using Drosophila melanogaster that illustrate the use of compound chromosomes to change the genetic structure of insect populations.
Citations
Possibilities of Insect Control or Eradication Through the Use of Sexually Sterile Males
E. F. Knipling, Journal of Economic Entomology, 48:459-462. 1955.
The purpose of this paper is to consider the possibility of controlling insects by releasing sexually sterile males among the existing natural population. The principles involved will be described and the potentialities as well as the limitations of the method as we know them at ...
Screw-worm control through release of sterilized flies
A. H. Baumhover, A. J. Graham, B. A. Bitter, D. E. Hopkins, W. D. New, F. H. Dudley and R. C. Bushland, Journal of Economic Entomology, 48:462-466. 1955.
Screw-worms, Callitroga hominivorax (Cqrl.), did not exist in the southeastern United States until about 20 years ago, and it is probable that, if the present infestation could be eradicated, the area might be kept free of infestation through inspection of livestock shipments ...
Studies of the genetic variability in populations of wild house mice .2. Analysis of eight additional alleles at locus – T
L. C. Dunn, Genetics, 42:299-311. 1957.
1 Eight additional lethal alleles at locus T are described, each derived from a wild heterozygote in one of six different wild populations. 2. The frequency of heterozygotes appears to be high in most wild populations, possibly as high as 50 percent. 3. In two of the ...
Inheritance in Nicotiana tabacum XXVII. Pollen Killer, An alien genetic locus inducing abortion of microspores not carrying it
D. R. Cameron and R. M. Moav, Genetics, 42:326. 1957.
A cytogenetic study of experimental introgression from N. plumbaginifolia (pbg) into N. tabacum (tbc) has been pursued in this laboratory for several years (CLAUSEN 1952). In the hybrid derivatives it was observed that genically controlled pollen abortion was associated with the ...
Meiotic drive as an evolutionary force
Sandler, L. and Novitski, E., American Naturalist, 91:105-110. 1957.
A heterozygote for alleles A and A' ordinarilly produces gametes carrying each of the alleles with a frequency of 50 per cent. The constancy of allele frequencies from one generation to the nest in natural populations of diploid species depends on this equality, which itself ...
Possible replacement of malaria mosquitoes
S. Avery Jones, Transactions of The Royal Society of Tropical Medicine and Hygiene, 51:469-470. 1957.
Sir,--The purpose of this letter is to draw the attention of research workers in control of mosquito colonies to the possible value of investigating the factors governing the infection of mosquitoes with parasites of human malaria. If a strain of a vector species could be ...
Meiotic drive in natural populations of Drosophila melanogaster .1. The cytogenetic basis of segregation distortion
Sandler, LH, Y.; Sandler, I., Genetics, 44:233-250. 1959.
Meiotic drive has been defined as a force, potentially capable of altering gene frequencies in natural populations, which somehow depends upon the nature of the meiotic divisions; specifically, when the meiotic divisions are such that the two kinds of gametes from a heterozygote ...
Inherited male-producing factor in Aedes aegypti
G. B. Craig, W. A. Hickey and R. C. Vandehey, Science, 132:1887-1889. 1960.
An inherited factor causes a predominance of males in certain strains and in progeny of single pairs of Aedes aegypti L. This factor appears to be transmitted only by males and is not due to differential mortality, at least in postgametic stages. Mass release of male-producing ...
On the role of lethal mutants in the control of populations
R. C. Von Borstel and A. A. Buzzati-Traverso, Radioisotopes and Radiation in Entomology: Proceedings of a Symposium, Bombay, 5-9 December, 1960, 1962:273-278. 1962.
On the role of lethal. mutants in the control of populations. Population control by release of irradiated males requires that the sperm must be damaged by radiation. The type of damage induced by radiation imposes a restriction on which species may be controlled because if the ...
Eradication of Culex pipiens fatigans through cytoplasmic incompatibility.
H. Laven, Nature, 216:383. 1967.
Culex pipiens fatigans is the chief vector of filariasis in south-east Asia. Urbanization has often caused the numbers of this mosquito-and with it the danger of filariasis infection-to increase alarmingly. The natural vigour, tolerance and fast development of resistance to ...
Possible use of translocations to fix desirable genes in insect populations.
Curtis, CF, Nature, 218:368-369. 1968.
Chromosome translocation heterozygotes (T/+) are usually semisterile, but translocation homozygotes (T/T) if viable are usually fully fertile. If such a viable translocation were produced in an insect pest, T/T insects could be reared in captivity and released into the wild, ...
Changing population structure through the use of compound chromosomes
D. Childress, Genetics, 72:183-186. 1972.
Theoretical calculations and population cage data are presented to illustrate the use of compound chromosomes to change the genetic structure of insect populations.
Genetic Control in Historical Perspective: The Legacy of India’s Genetic Control of Mosquitoes Unit
R. Wilbanks, Hastings Center Report, 51:S11-S18. 2021.
Abstract In the early 1970s, a World Health Organization-initiated and United States-funded project released lab-reared mosquitoes outside New Delhi in the first large-scale field trials of the genetic control of mosquitoes. Despite partnering with the Indian Council of Medical ...1975 - 2000
Molecular Genetic & Transgenic TechnologiesChristopher Curtis (1939 – 2008)
Explored genetic control of insect vectors of human pathogens and parasitesThe emergence of molecular genetic technologies including transgenic technologies for insects, animals and plants motivated interests in genetic biocontrol technologies. Transposable elements were major platforms for genetic engineering technologies and were considered possible systems for introducing and spreading (‘driving’) transgenes into selected populations of harmful insects.
Curtis (1976) reports the first field cage experiment testing a gene drive system based on cytoplasmic incompatibility in the mosquito Culex fatigans.
Wood et al (1977) successfully use a natural meiotic drive system in the mosquito Aedes aegypti to drive an allele of the redeye gene into laboratory cage populations.
Lyttle (1977) experimentally demonstrates the use of a ‘pseudo-Y’ drive to eliminate cage populations of Drosophila melanogaster.
Graves and Curtis (1982) report an early experimental attempt in laboratory populations of Anopheles mosquitoes to replace malaria susceptibility with refractoriness (malaria resistance). These experiments were conducted without the use of a ‘drive’ system.
Rubin and Spradling (1982) report their invention of the first transgenic insect technology. It uses a trasposable element platform and they used it to create transgenic fruitflies, Drosophila melanogaster.
Good et al (1989) demonstrate experimentally how the transposable element P from Drosophila melanogaster could rapidly spread in laboratory populations of Drosophila melanogaster.
Kidwell and Ribeiro (1992) review and explain how transposable elements could be used to drive genes of interest into populations of insects.
Curtis and Sinkins (1998) propose the use of Wolbachia as a gene drive.
Loukeris et al (1995) report the creation of the first transgenic insect that was not a species of Drosophila. The technology for creating transgenic Drosophila was limited to insects of that genus. Loukeris (1995) report the creation of transgenic Mediterranean fruitfly, Ceratitis capitata, using a new, more robust and species-independent transposable element-based technology.
Coates et al. (1998) and Jasinskiene (1998) report on the creation of the first transgenic mosquitoes (Aedes aegypti) using two newly developed transposable element-based technologies with few species limitations.
Citations
Population replacement in Culex-fatigans by means of cytoplasmic incompatibility .2. Field cage experiments with overlapping generations
C. F. Curtis, Bulletin of the World Health Organization, 53:107-119. 1976.
Three experiments were carried out in field cages to test the principle of " transport" of a desirable gene or chromosome into a wild Culex fatigans population as a result of the sterility in cross-matings associated with cytoplasmic incompatibility. Cycling populations of Delhi ...
Experimental population-genetics of meiotic drive systems .1: Pseudo-Y chromosomal drive as a means of eliminating cage populations of Drosophila melanogaster
Lyttle, TW, Genetics, 86:413-445. 1977.
The experimental population genetics of Y-chromosome drive in Drosophila; melanogasier is approximated by studying the behavior of T(Y;S),SD lines.; These exhibit “pseudo-Y” drive through the effective coupling of the Y chromosome; to the second chromosome meiotic drive ...
Transporting marker gene re (red eye) into a laboratory cage population of Aedes-aegypti (Diptera Culicidae), using meiotic drive at MD locus
R. J. Wood, L. M. Cook, A. Hamilton and A. Whitelaw, Journal of Medical Entomology, 14:461-464. 1977.
An attempt has been made to use the meiotic drive gene MD to transport a marker re (redeye) into a laboratory population of the mosquito Aedes aegypti. The experiment produced an increase in re frequency, but also indicated that this gene has unexpectedly high fitness in the ...
Rapid spread of transposable P elements in experimental populations of Drosophila melanogaster.
A. G. Good, G. A. Meister, H. W. Brock, T. A. Grigliatti and D. A. Hickey, Genetics, 1223:387-396. 1989.
The invasion of P elements in natural populations of Drosophila melanogaster was modeled by establishing laboratory populations with 1 %, 5% and 10% P genomes and monitoring the populations for 20 generations. In one experiment, the ability of flies to either induce or suppress ...
Can transposable elements be used to drive disease refractoriness genes into vector populations?
M. G. Kidwell and J. M. C. Ribeiro, Parasitology Today, 8:325-329. 1992.
A number of biological procedures are currently being considered as alternatives to insecticide-based methods for the control of insect vectors of disease. Among these are the adaptation of various genetic mechanisms to drive genes of interest, such as refractoriness to malaria ...
Gene transfer into the Medfly, Ceratitis capitata, using a Drosophila hydei transposable element.
T. G. Loukeris, I. Livadaras, B. Arca, S. Zabalou and C. Savakis, Science, 270:2002-2005. 1995.
Exogenous functional DNA was introduced into the germline chromosomes of the Mediterranean fruit fly (medfly) Ceratitis capitata with a germline transformation system based on the transposable element Minos from Drosophila hydei. Transformants were identified as phenotypic ...
Wolbachia as a possible means of driving genes into populations
Curtis, CFS, S. P., Parasitology, 116:S111-S115. 1998.
Cytoplasmic incompatibility consists of sterility in cross matings, the crossing type being maternally inherited. It can be explained by the action of Wolbachia symbionts which are transmitted through the egg cytoplasm and leave an imprint on the sperm which prevents it ...
Stable transformation of the yellow fever mosquito, Aedes aegypti, with the Hermes element from the housefly
N. Jasinskiene, C. J. Coates, M. Q. Benedict, A. J. Cornel, C. S. Rafferty, A. A. James and F. H. Collins, Proceedings of the National Academy of Sciences of the United States of America, 95:3743-3747. 1998.
The mosquito Aedes aegypti is the world's most important vector of yellow fever and dengue viruses, Work is currently in progress to control the transmission of these viruses by genetically altering the capacity of wild Ae, aegypti populations to support virus replication. The ...
Mariner transposition and transformation of the yellow fever mosquito, Aedes aegypti
C. J. Coates, N. Jasinskiene, L. Miyashiro and A. A. James, Proceedings of the National Academy of Sciences of the United States of America, 95:3748-3751. 1998.
The mariner transposable element is capable of interplasmid transposition in the embryonic soma of the yellow fever mosquito, Aedes aegypti. To determine if this demonstrated mobility could be utilized to genetically transform the mosquito, a modified mariner element marked with ...2000 - today
Gene Editing TechnologiesAustin Burt
First proposed the use of homing endonucleases as gene drive platformsThere was a decided shift away from gene drive systems based on transposable elements in favor of more active and efficient homing endonucleases (meganucleases) and, more recently, RNA programmable DNA endonucleases such as those associated with CRISPR systems found in bacteria.
Burt (2003) proposes that homing endonucleases could be useful platforms for creating active gene drive systems.
Chen et al (2007) create a synthetic cytoplasmic incompatability gene drive system in Drosophila melanogaster based on maternal-effect selfish genetic elements known as Medea found in flour beetles and show its ability to efficiently drive to high frequencies in laboratory populations.
Windbichler et al (2007) describe successful gene targeting in cells and embryos of the human malaria vector, Anopheles gambiae, using a homing endonuclease.
Windbichler et al (2011) report the successful creation of the first engineered gene drive system in the human malaria vector Anopheles gambiae. This meiotic drive system resulted in a distortion of the sex ratio strongly in favor of males.
Harris et al (2011) report the first open field trial of a genetically modified mosquito – Aedes aegypti.
Esvelt et al (2014) first published report of using programmable RNA dependent DNA endonucleases such as Cas9, from the CRISPR system of Streptococcus pyogenes, to serve as versatile platforms for the creation of homing endonuclease-like gene drive systems.
DiCarlo et al (2015) report the creation of the first engineered homing-endonuclease-like gene drive system using the programmable RNA dependent DNA endonuclease, Cas9. They create and test their system in the laboratory using the yeast, Saccharomyces cerevisiae.
Gantz and Bier (2015) create a gene drive system based on the programmable RNA dependent DNA endonuclease, Cas9, from the CRISPR system of Streptococcus pyogenes and demonstrate its effectiveness in the fruit fly, Drosophila melanogaster, in the laboratory.
Gantz et al (2015) create a gene drive system in the human malaria vector Anopheles stephensi using the programmable RNA dependent DNA endonuclease, Cas9, from the CRISPR system of Streptococcus pyogenes.
U.S. National Academies of Sciences, Engineering, and Medicine (2016) publish their recommendations for the responsible conduct of gene drive research in non-human organisms.
Hammond et al (2016) create a sex ratio distorting meiotic drive (gene drive) system in the human malaria vector, Anopheles gambiae, using the programmable RNA dependent DNA endonuclease, Cas9, from the CRISPR system of Streptococcus pyogenes.
Kyrou et al (2018) demonstrate engineered gene drive mediated population suppression in laboratory cages containing the human malaria vector, Anopheles gambiae.
Grunwald et. al (2019) introduce an engineered gene drive into the house mouse, Mus musculus, in the laboratory.
Citations
Site-specific selfish genes as tools for the control and genetic engineering of natural populations
Burt, A, Proceedings of the Royal Society B-Biological Sciences, 270:921-928. 2003.
Site-specific selfish genes exploit host functions to copy themselves into a defined target DNA sequence, and include homing endonuclease genes, group II introns and some LINE-like transposable elements. If such genes can be engineered to target new host sequences, then they can ...
A synthetic maternal-effect selfish genetic element drives population replacement in Drosophila
Chen, CHH, H. X.; Ward, C. M.; Su, J. T.; Schaeffer, L. V.; Guo, M.; Hay, B. A., Science, 316:597-600. 2007.
One proposed strategy for controlling the transmission of insect-borne pathogens uses a drive mechanism to ensure the rapid spread of transgenes conferring disease refractoriness throughout wild populations. Here, we report the creation of maternal-effect selfish genetic elements ...
Homing endonuclease mediated gene targeting in Anopheles gambiae cells and embryos
Windbichler, NP, P. A.; Catteruccia, F.; Ranson, H.; Burt, A.; Crisanti, A., Nucleic Acids Research, 35:5922-5933. 2007.
Homing endonuclease genes (HEGs) are selfish genetic elements that combine the capability to selectively disrupt specific gene sequences with the ability to rapidly spread from a few individuals to an entire population through homologous recombination repair events. Because of ...
A synthetic homing endonuclease-based gene drive system in the human malaria mosquito
Windbichler, NM, M.; Papathanos, P. A.; Thyme, S. B.; Li, H.; Ulge, U. Y.; Hovde, B. T.; Baker, D.; Monnat, R. J.; Burt, A.; Crisanti, A., Nature, 473:212-215. 2011.
Genetic methods of manipulating or eradicating disease vector populations have long been discussed as an attractive alternative to existing control measures because of their potential advantages in terms of effectiveness and species specificity(1-3). The development of ...
Field performance of engineered male mosquitoes
A. F. Harris, D. Nimmo, A. R. McKemey, N. Kelly, S. Scaife, C. A. Donnelly, C. Beech, W. D. Petrie and L. Alphey, Nature Biotechnology, 29:1034-1037. 2011.
Mass-release of sterile male mosquitoes is a promising option for controlling dengue and malaria, but it has never been shown that lab-raised transgenic males can compete effectively with their wild counterparts outside laboratory conditions. Promising results from a restricted ...
Field performance of engineered male mosquitoes
A. F. Harris, D. Nimmo, A. R. McKemey, N. Kelly, S. Scaife, C. A. Donnelly, C. Beech, W. D. Petrie and L. Alphey, Nature Biotechnology, 29:1034-1037. 2011.
Mass-release of sterile male mosquitoes is a promising option for controlling dengue and malaria, but it has never been shown that lab-raised transgenic males can compete effectively with their wild counterparts outside laboratory conditions. Promising results from a restricted ...
Concerning RNA-guided gene drives for the alteration of wild populations
Esvelt, KMS, Andrea L.; Catteruccia, Flaminia; Church, George M., eLife, 3:e03401. 2014.
Gene drives may be capable of addressing ecological problems by altering entire; populations of wild organisms, but their use has remained largely theoretical due to technical; constraints. Here we consider the potential for RNA-guided gene drives based on the CRISPR; nuclease ...
The mutagenic chain reaction: A method for converting heterozygous to homozygous mutations
V. M. Gantz and E. Bier, Science, 348:442. 2015.
Loss-of-function mutations may only produce a mutant phenotype when both copies of the gene are mutated. Gantz and Bier developed a method they call mutagenic chain reaction (MCR) that autocatalytically produces homozygous mutations. MCR uses the initial mutated allele to cause a ...
A CRISPR-Cas9 gene drive system-targeting female reproduction in the malaria mosquito vector Anopheles gambiae
Hammond, AG, R.; Kyrou, K.; Simoni, A.; Siniscalchi, C.; Katsanos, D.; Gribble, M.; Baker, D.; Marois, E.; Russell, S.; Burt, A.; Windbichler, N.; Crisanti, A.; Nolan, T., Nature Biotechnology, 34:78-83. 2016.
Gene drive systems that enable super-Mendelian inheritance of a transgene have the potential to modify insect populations over a timeframe of a few years. We describe CRISPR-Cas9 endonuclease constructs that function as gene drive systems in Anopheles gambiae, the main vector for ...
Gene Drives on the Horizon: Advancing Science, Navigating Uncertainty, and Aligning Research with Public Values
U. S. National Academies of Sciences, Engineering, and Medicine, The National Academies Press, 2016.
Scientists have studied gene drives for more than 50 years. The development of a powerful genome editing tool in 2012, CRISPR/Cas9,1 led to recent breakthroughs in gene drive research that built on that half century’s worth of knowledge, and stimulated new discussion of the ...
A CRISPR–Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes
Kyrou, KH, Andrew M.; Galizi, Roberto; Kranjc, Nace; Burt, Austin; Beaghton, Andrea K.; Nolan, Tony; Crisanti, Andrea, Nature Biotechnology, 36:1062–1066. 2018.
In the human malaria vector Anopheles gambiae, the gene doublesex (Agdsx) encodes two alternatively spliced transcripts, dsx-female (AgdsxF) and dsx-male (AgdsxM), that control differentiation of the two sexes. The female transcript, unlike the male, contains an exon (exon 5) ...
Super-Mendelian inheritance mediated by CRISPR-Cas9 in the female mouse germline
Grunwald, HAG, V. M.; Poplawski, G.; Xu, X. R. S.; Bier, E.; Cooper, K. L., Nature, 566:105-109. 2019.
A gene drive biases the transmission of one of the two copies of a gene such that it is inherited more frequently than by random segregation. Highly efficient gene drive systems have recently been developed in insects, which leverage the sequence-targeted DNA cleavage activity of ...
