Details:

Alternative Title:
ACS Synth Biol
Publisher's site:
http://dx.doi.org/10.1021/sb300079h
Personal Author:
Akbari, Omar S. ; Chen, Chun-Hong ; Marshall, John M. ; Huang, Haixia ; Antoshechkin, Igor ; ... More +
Akbari, Omar S. ; Chen, Chun-Hong ; Marshall, John M. ; Huang, Haixia ; Antoshechkin, Igor ; Hay, Bruce A. Less -
Description:
Insects act as vectors for diseases of plants, animals, and humans. Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a potentially self-perpetuating method of disease prevention. Population replacement requires a gene drive mechanism in order to spread linked genes mediating disease refractoriness through wild populations. We previously reported the creation of synthetic Medea selfish genetic elements able to drive population replacement in Drosophila. These elements use microRNA-mediated silencing of myd88, a maternally expressed gene required for embryonic dorso-ventral pattern formation, coupled with early zygotic expression of a rescuing transgene, to bring about gene drive. Medea elements that work through additional mechanisms are needed in order to be able to carry out cycles of population replacement and/or remove existing transgenes from the population, using second-generation elements that spread while driving first-generation elements out of the population. Here we report the synthesis and population genetic behavior of two new synthetic Medea elements that drive population replacement through manipulation of signaling pathways involved in cellular blastoderm formation or Notch signaling, demonstrating that in Drosophila Medea elements can be generated through manipulation of diverse signaling pathways. We also describe the mRNA and small RNA changes in ovaries and early embryos associated from Medea-bearing females. Finally, we use modeling to illustrate how Medea elements carrying genes that result in diapause-dependent female lethality could be used to bring about population suppression.
Subject:
[+]
Animals
Article
Dengue
Drosophila
Female
Gene Drive
Genetic Engineering
Malaria
Male
Maternal-effect
Models, Genetic
Mosquito
Repetitive Sequences, Nucleic Acid
Selfish Genetic Element
Synthetic Biology
Synthetic Biology

Source:
ACS Synth Biol. 3(12):915-928.
Pubmed ID:
23654248
Pubmed Central ID:
PMC3742681
Document Type:
Journal Article
Funding:
DP1 GM105377/GM/NIGMS NIH HHS/United States ; DP10D003878/DP/NCCDPHP CDC HHS/United States ; Medical Research Council/United Kingdom
DP1 GM105377/GM/NIGMS NIH HHS/United States ; DP10D003878/DP/NCCDPHP CDC HHS/United States ; Medical Research Council/United Kingdom Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:3011c79b55165eddfce92daef796528722e6f0690ffa224dfc0d7c9c79811b62
File Type:

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