Por Mauro Rebelo

Theoretical model of the mussel gene-drive

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To draw up the proposal, the Bio Bureau developed the theoretical model, which characterizes the 2nd stage on the TRL scale, based on the gene-drive for controlling the malaria vector (Anopheles gambiae) that was being developed by Andrea Crisanti’s group at Imperial College London.

In this model, we would silence a mussel’s reproductive gene by inserting a (long) DNA fragment (construct) into the middle of its sequence, which encodes a set of enzymes capable of replicating this fragment and inserting it into the unmodified allele of the same reproductive gene on another chromosome.

Self-replication of the construct and self-insertion into an unmodified copy allow this trait (infertility) to spread through the population at a faster rate than that expected by conventional Mendelian inheritance. This is why it is called super-Mendelian inheritance. Or Gene-Drive.

The assumptions were validated with Andrea Crisanti himself, who is the project’s scientific advisor.

The description of the model was formalized in an article published in pre-print format in 2018.

  • Rebelo MF, Afonso LF, Americo JA, da Silva L, Neto JLB, Dondero F, Zhang Q. 2018. A sustainable synthetic biology approach for the control of the invasive golden mussel (Limnoperna fortunei) PeerJ Preprints6:e27164v3 https://doi.org/10.7287/peerj.preprints.27164v3

See also the article that inspired our project:

  • 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. (2016). A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nature Biotechnology, 34(1), 78-83. https://doi.org/10.1038/nbt.3439

 

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Tags: TRL#2