population genetic engineering
- A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae.
Hammond A, Galizi 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. 2016 Jan;34(1):78-83. doi: 10.1038/nbt.3439. Epub 2015 Dec 7.
In this paper we showed that RNA-guided endonucleases based on the CRISPR-Cas9 system can efficiently home and spread. We targeted female fertility genes and showed that genetic drive of the CRISPR homing endonuclease could be used to supresss pest population.
Simoni A, Siniscalchi C, Chan YS, Huen DS, Russell S, Windbichler N, Crisanti A.
Nucleic Acids Research. 2014 May 6. PubMed PMID: 24803674.
In this paper we showed that both TALEN and Zinc-finger endonucleases can spread by homing. This suggested that any sufficiently-specific endonuclease could be used for population genetic engineering.
Windbichler N, Menichelli M, Papathanos PA, Thyme SB, Li H, Ulge UY, Hovde BT, Baker D, Monnat RJ Jr, Burt A, Crisanti A.
Nature. 2011 May 12;473(7346):212-5. doi: 10.1038/nature09937. Epub 2011 Apr 20. PubMed PMID: 21508956
In this paper we introduced a homing endonuclease gene into the genome of the human malaria vector Anopheles gambiae. We were able to show that this gene is able to function in the germline of animals and that the gene can rapidly invade receptive mosquito cage populations. These findings demonstrate the first “gene drive” mechanism by which genetic mosquito control measures could be implemented. The paper shows, in practice, how the step from the genetic engineering of individuals to the genetic engineering of entire populations can be taken.
Windbichler N, Papathanos PA, Catteruccia F, Ranson H, Burt A, Crisanti A.
Nucleic Acids Research. 2007;35(17):5922-33. Epub 2007 Aug 28. PubMed PMID: 17726053
Although they don't exist in metazoa, we showed that a class of naturally occuring selfish genes called homing endonuclease genes could function and spread in animals.
sex ratio distortion as a tool for genetic control
Galizi R, Hammond A, Kyrou K, Taxiarchi C, Bernardini F, O'Loughlin SM, Papathanos PA, Nolan T, Windbichler N, Crisanti A.
Scientific Reports. 2016 Aug 3;6:31139. doi: 10.1038/srep31139.
Bernardini F, Galizi R, Menichelli M, Papathanos PA, Dritsou V, Marois E, Crisanti A, Windbichler N.
PNAS. 2014 May 27;111(21):7600-5. doi: 10.1073/pnas.1404996111. PMID: 24821795
We showed that in the malaria mosquito the heterochromatic Y-chromsome is amenable to genetic modification and transgene expression, a first step towrads genrating Y-linked X-shredders.
Galizi R, Doyle LA, Menichelli M, Bernardini F, Deredec A, Burt A, Stoddard BL, Windbichler N, Crisanti A.
Nature Communications. 2014 Jun 10;5:3977. doi: 10.1038/ncomms4977. PubMed PMID: 24915045
We showed that in the malaria mosquito destabilized variants of the naturally occuring endonuclease I-PpoI could distort the reporductive sex ratio of the progeny towards males without affecting male fertility. This is the basis for a new class of genetic control.
- Targeting the X chromosome during spermatogenesis induces Y chromosome transmission ratio distortion and early dominant embryo lethality in Anopheles gambiae.
Windbichler N, Papathanos PA, Crisanti A.
PLoS Genetics. 2008 Dec;4(12):e1000291. doi: 10.1371/journal.pgen.1000291. Epub 2008 Dec 5. PubMed PMID: 19057670
This paper was first to demonstrate that, by destroying it during male meisois by a highly-specific endonuclease, the transmission of the X-chromsome to the proogeny could be prevented thus favouring the Y-chromsome bearing gametes.
Andrew Brantley Hall, Philippos-Aris Papathanos, Atashi Sharma, Changde Cheng, Omar S. Akbari, Lauren Assour, Nicholas H. Bergman, Alessia Cagnetti, Andrea Crisanti, Tania Dottorini, Elisa Fiorentini, Roberto Galizi, Jonathan Hnath, Xiaofang Jiang, Sergey Koren, Tony Nolan, Diane Radune, Maria V. Sharakhova, Aaron Steele, Vladimir A. Timoshevskiy, Nikolai Windbichler, Simo Zhang, Matthew W. Hahn, Adam M. Phillippy, Scott J. Emrich, Igor V. Sharakhov, Zhijian Jake Tu, and Nora J. Besansky'
PNAS. March 29, 2016, doi: 10.1073/pnas.1525164113
Magnusson K, Lycett GJ, Mendes AM, Lynd A, Papathanos PA, Crisanti A, Windbichler N.
BMC Evolutionary Biology. 2012 May 18;12:69. doi: 10.1186/1471-2148-12-69. PubMed PMID: 22607633