Integral gene drives for population replacement
A first generation of CRISPR-based gene drives has now been tested in the laboratory in a number of organisms, including malaria vector mosquitoes. Challenges for their use in the area-wide genetic control of vector-borne disease have been identified, including the development of target site resista...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2019-01-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/8/1/bio037762 |
| _version_ | 1819075582178099200 |
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| author | Alexander Nash Giulia Mignini Urdaneta Andrea K. Beaghton Astrid Hoermann Philippos Aris Papathanos George K. Christophides Nikolai Windbichler |
| author_facet | Alexander Nash Giulia Mignini Urdaneta Andrea K. Beaghton Astrid Hoermann Philippos Aris Papathanos George K. Christophides Nikolai Windbichler |
| author_sort | Alexander Nash |
| collection | DOAJ |
| description | A first generation of CRISPR-based gene drives has now been tested in the laboratory in a number of organisms, including malaria vector mosquitoes. Challenges for their use in the area-wide genetic control of vector-borne disease have been identified, including the development of target site resistance, their long-term efficacy in the field, their molecular complexity, and practical and legal limitations for field testing of both gene drive and coupled anti-pathogen traits. We have evaluated theoretically the concept of integral gene drive (IGD) as an alternative paradigm for population replacement. IGDs incorporate a minimal set of molecular components, including drive and anti-pathogen effector elements directly embedded within endogenous genes – an arrangement that in theory allows targeting functionally conserved coding sequences without disrupting their function. Autonomous and non-autonomous IGD strains could be generated, optimized, regulated and imported independently. We performed quantitative modeling 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 drive occurring at multiple genomic loci prolongs the duration of transmission blockage in the face of pre-existing target site variation. IGD thus has potential as a more durable and flexible population replacement strategy. |
| first_indexed | 2024-12-21T18:27:42Z |
| format | Article |
| id | doaj.art-a12c7d2743e94064966ae06e8026740b |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-21T18:27:42Z |
| publishDate | 2019-01-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-a12c7d2743e94064966ae06e8026740b2022-12-21T18:54:23ZengThe Company of BiologistsBiology Open2046-63902019-01-018110.1242/bio.037762037762Integral gene drives for population replacementAlexander Nash0Giulia Mignini Urdaneta1Andrea K. Beaghton2Astrid Hoermann3Philippos Aris Papathanos4George K. Christophides5Nikolai Windbichler6 Department of Life Sciences, Imperial College London, Sir Alexander Fleming Building, South Kensington Campus, London SW7 2AZ, UK Department of Life Sciences, Imperial College London, Sir Alexander Fleming Building, South Kensington Campus, London SW7 2AZ, UK Department of Life Sciences, Imperial College London, Sir Alexander Fleming Building, South Kensington Campus, London SW7 2AZ, UK Department of Life Sciences, Imperial College London, Sir Alexander Fleming Building, South Kensington Campus, London SW7 2AZ, UK Centre of Functional Genomics, Department of Experimental Medicine, University of Perugia, Perugia 06123, Italy Department of Life Sciences, Imperial College London, Sir Alexander Fleming Building, South Kensington Campus, London SW7 2AZ, UK Department of Life Sciences, Imperial College London, Sir Alexander Fleming Building, South Kensington Campus, London SW7 2AZ, UK A first generation of CRISPR-based gene drives has now been tested in the laboratory in a number of organisms, including malaria vector mosquitoes. Challenges for their use in the area-wide genetic control of vector-borne disease have been identified, including the development of target site resistance, their long-term efficacy in the field, their molecular complexity, and practical and legal limitations for field testing of both gene drive and coupled anti-pathogen traits. We have evaluated theoretically the concept of integral gene drive (IGD) as an alternative paradigm for population replacement. IGDs incorporate a minimal set of molecular components, including drive and anti-pathogen effector elements directly embedded within endogenous genes – an arrangement that in theory allows targeting functionally conserved coding sequences without disrupting their function. Autonomous and non-autonomous IGD strains could be generated, optimized, regulated and imported independently. We performed quantitative modeling 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 drive occurring at multiple genomic loci prolongs the duration of transmission blockage in the face of pre-existing target site variation. IGD thus has potential as a more durable and flexible population replacement strategy.http://bio.biologists.org/content/8/1/bio037762Gene drivePopulation replacementCRISPRGenome editingPopulation modeling |
| spellingShingle | Alexander Nash Giulia Mignini Urdaneta Andrea K. Beaghton Astrid Hoermann Philippos Aris Papathanos George K. Christophides Nikolai Windbichler Integral gene drives for population replacement Biology Open Gene drive Population replacement CRISPR Genome editing Population modeling |
| title | Integral gene drives for population replacement |
| title_full | Integral gene drives for population replacement |
| title_fullStr | Integral gene drives for population replacement |
| title_full_unstemmed | Integral gene drives for population replacement |
| title_short | Integral gene drives for population replacement |
| title_sort | integral gene drives for population replacement |
| topic | Gene drive Population replacement CRISPR Genome editing Population modeling |
| url | http://bio.biologists.org/content/8/1/bio037762 |
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