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UCIMI hosts annual meeting on February 1-2, 2021
Over 67 scientists from five different countries were in attendance for this year’s annual UCIMI meeting held online via Zoom. Attendees received reports on the UCIMI research program’s efforts in laboratory sciences, community engagement, field work, as well as modeling reports from our collaborating field site countries in Sao Tome and Principe and the Union of the Comoros.
Meeting highlights included reports on gene-drive systems, anti-parasite effector molecules, population genetic analysis of potential wild target mosquitoes, updates on malaria status and project activities in collaborating partner countries and detailed modelling of vector dynamics and disease epidemiology. Additional details are below, as well as a full list of UCIMI related 2019-2020 publications.
- A robust gene-drive strain, AgNosCd1, for population modification of the African malaria mosquito, Anopheles gambiae, was developed and will allow rapid and efficient introduction of beneficial traits (anti-parasite effector genes) within a single malaria transmission season. See Carballar-Lejarazú et al. 2020.
- AgNosCd1 shows strong drive when introduced into geographically-distinct gambiae strains and is therefore expected to perform well in wild mosquito populations.
- AgNosCd1 has strong drive when introgressed into the sibling species, coluzzii, allowing targeting malaria where this species contributes to disease-transmission dynamics.
- More than 20 different transgenic mosquito strains that either over-express anti-parasite effector genes or have mutated host factor genes were evaluated for resistance to Plasmodium falciparum and fitness parameters providing essential information on the potency of different transgenes in blocking parasites. See Dong et al., 2020.
- Seven transgenic mosquito strains meet Plasmodium blocking thresholds predicted to have an epidemiologically-significant impact on malaria transmission with at least two of the strains, one carrying a single amino acid polymorphism of the FREP1 gene product and one carrying dual anti-pathogen, single chain antibodies, are in the development pipeline for field-trial evaluation.
- Research with the Indo-Pakistan malaria vector, stephensi, informed small-cage trial designs and alternate modes for managing drive-resistant target sites. See Pham et al., 2019; Adolfi et al., 2020.
- Hybridization in situ analysis documented the expression profiles of the AgNosCd1 nanos-Cas9 and stephensi vasa-Cas9 transgenes validating parameters of the target product profile and regulatory portfolio.
- Split, recoded gene-drive systems provide a general solution to the production of drive-resistant alleles and can be adapted to varying degrees of drive and confinement potential, making them suitable to deliver a pulse of genetic modification to a population.
- Allelic drive systems targeting essential genes can reverse insecticide resistance rendering populations susceptible to being controlled once again with pesticides.
- Malaria transmission in the Union des Comores (Comoros) is currently low because of different control strategies implemented by the Malaria Control Program (PNLP).
- Achievements for the Malaria Program in 2020 in the República Democrática de São Tomé e Príncipe (STP) included a reduction in malaria cases compared to 2019; creation of an emergency response plan for increased malaria cases late in 2020, and an educational community campaign for malarial control in all health areas/districts.
- The island mosquito fauna of STP and the Comoros are characterized by significantly fewer Anopheles species when compared with the mainland.
- More than 800 individual gambiae and An. coluzzii individual insect genomes were sequenced. See Schmidt et al. 2019.
- The island populations of An. gambiae and An. coluzzii are genetically-isolated from mainland populations and carry significantly lower nucleotide polymorphism compared to mainland populations.
- Candidate Cas9/guide-RNA target sites are abundant and conserved within the genomes of gambiae and An. coluzzii. See Schmidt et al. 2019.
- A modeling framework, Mosquito Gene Drive Explorer 2 (freely available at MGDrivE 2) was developed with modules for: i) inheritance, ii) mosquito life history, iii) landscape, and iv) epidemiology. The model is responsive to seasonal changes in temperature and rainfall. See Wu et al. 2020.
- Sample model outputs demonstrate the potential for reduction in human malaria incidence following releases of a homing-based gene drive system in gambiae on the island of Grand Comore.
- Homing-based gene drive models were fitted to small-cage trial data for the Indo-Pakistan malaria vector, stephensi. See Pham et al., 2019; Adolfi et al., 2020.
- Preliminary models have been developed for the distribution of mosquito habitat and movement among habitat nodes in STP and Comoros.
- Statistical and cluster analyses were conducted to characterize malaria transmission in STP and better understand the impact of currently-used interventions.
- Virtual (on-line) monthly meetings were held with the National Malaria Control Programs in both STP and Comoros, and several information-sharing workshops with stakeholder groups in STP.
- An operational contract and budget with the United Nations Development Program in STP was finalized to facilitate the recruitment, hiring and management of local personnel for the UCIMI project.
- Approval from the STP Ministry of Health in was granted to initiate regulatory engagement and hire a local regulatory consultant to assist in the development of a plan for obtaining regulatory approval for planning field trials.
- A relationship-based model for engagement was adopted. See Kormos et al., 2020.
- UCIMI scientists continue to contribute to local and global outreach and education on new genetic technologies. See Kelsey et al., 2020; Cheung et al., 2020
2019-2020 UCIMI-related open access publications (and active links) in Annual report:
• Adolfi. et al. (2020) A population modification gene-drive rescue system dominantly eliminates resistance alleles in the malaria mosquito, Anopheles Stephensi. Nature Comm.
• Carballar-Lejarazú et al. (2020) Digital droplet PCR and IDAA for the detection of CRISPR indel edits in the malaria species Anopheles Stephensi
• Carballar-Lejarazú et al. (2020) Next-generation gene drive for population modification of the vector mosquito, Anopheles gambiae. Proc. Natl. Acad. Sci. USA.
• Cheung., et al. (2020) Translating gene drive science to promote linguistic diversity in community and stakeholder engagement. Glob Public Health.
• Dong et al. (2020) Versatile transgenic multistage effector-gene combinations for Plasmodium falciparum suppression in Anopheles. Sci. Adv.
• James et al. (2020) Toward the definition of efficacy and safety criteria for advancing gene drive-modified mosquitoes to field testing. Vector-Borne and Zoonotic Diseases.
• Kelsey et al. (2020) Global Governing Bodies: A Pathway for Gene Drive Governance for Vector Mosquito Control. J. Am. Soc. Trop. Med. Hyg.
• Kormos, et al. (2020) Application of the Relationship-Based Model to Engagement for Field Trials of Genetically Engineered Malaria Vectors
J. Am. Soc. Trop. Med. Hyg.
• Lee et al. (2020) Evidence for Divergent Selection on Immune Genes between the African Malaria Vectors, Anopheles Coluzzii and A. Gambiae. Insects.
• Marshall et al. (2019) Winning the Tug-of-War Between Effector Gene Design and Pathogen Evolution in Vector Population Replacement Strategies. Frontiers in Genetics.
• Pham et al. (2019) Experimental population modification of the malaria vector mosquito, Anopheles Stephensi. PLoS Genetics.
• Sánchez al. (2019) MGDrivE: A modular simulation framework for the spread of gene drives
through spatially explicit mosquito populations. Methods in Ecology and Evolution.
• Schmidt et al. (2019) Abundance of conserved CRISPR-Cas9 target sites within the highly polymorphic genomes of Anopheles and Aedes
mosquitoes. Nature Comm.
• Wu et al. (2020) MGDrivE 2: A simulation framework for gene drive systems incorporating seasonality and epidemiological dynamics. PLoS Computational Biology.
• Xu et al. (2020) Active Genetic Neutralizing Elements for Halting or Deleting Gene Drives. Molecular Cell.
UCIMI SCIENTIFIC REPORTS & PUBLICATIONS
Find information here about the malaria research that the UCIMI team has published.
- Abundance of conserved CRISPR-Cas9 target sites within the highly polymorphic genomes of Anopheles and Aedes mosquitoes. / Schmidt H.(2020)
- Experimental population modification of the malaria vector mosquito, Anopheles stephensi. / Pham TB (2019)
- Population modification of Anopheline species to control malaria transmission. / Carballar-Lejarazú, R (2018)
- Two lines of research converge to create immunizing gene-drive mosquitoes. / Bier E. (2017)
- Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi. /Gantz VM et al (2015)
- Evaluation of potential field trial sites for the release of genetically engineered mosquitoes. Hanemaaijer MJ et al (2018)
- Gene Drives and Active Genetics in The Biomedical & Life Sciences Collection, Henry Stewart Talks.
- Engineered Resistance to Plasmodium falciparum Development in Transgenic Anopheles stephensi / Isaac et al (2011)
- Transgenic Anopheles stephensi coexpressing single-chain antibodies resist Plasmodium falciparum development / Issac et al (2012)
- Chapter 19. Impact of Genetic Modification of Vector Populations on the Malaria Eradication Agenda, by Vanessa Macias and Anthony A James / Macias et al (2015)
- MGDrivE: A modular simulation framework for the spread of gene drives through spatially-explicit mosquito populations. / Sánchez HM (2020)
- Active Genetic Neutralizing Elements for Halting or Deleting Gene Drives / Xu X.S. (2020)
- Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi / A. Adolfi (2020)
- Application of the Relationship-Based Model to Engagement for Field Trials of Genetically Engineered Malaria Vectors / Kormos A. (2020)
- The origin of island populations of the African malaria mosquito, Anopheles coluzzii / Campos M, et al. (2021)
- Population modification strategies for malaria vector control are uniquely resilient to observed levels of gene drive resistance alleles / Lanzaro, G.C. et al. (2021)
- Gene Drives Gaining Speed / Bier E. (2021)
- Selection of sites for field trials of genetically engineered mosquitoes with gene drive / Lanzaro G.C. (2021)
EXTERNAL REPORTS AND PUBLICATIONS
Links to malaria related reports and publications from international partners, organizations, and the malaria research community.
- Gene drives on the horizon: Advancing science, navigating uncertainty, and aligning research with public values / National Academies
of Science, Engineering and Medicine
- Guidance framework for testing of genetically modified mosquitoes / World Health Organization
- Pathway to Deployment of Gene Drive Mosquitoes as a Potential Biocontrol Tool for Elimination of Malaria in Sub-Saharan Africa:
Recommendations of a Scientific Working Group
- WHO 2019 world malaria report
- WHO Global technical strategy for malaria
- Malaria eradication: benefits, future scenarios & feasibility
- Toward the definition of efficacy and safety criteria for advancing gene drive-modified mosquitoes to field testing. / James SL, Marshall JM, Christophides GK, Okumu FO, Nolan T (2020)
- Strengthening AU Member States’ Regulatory Capacities for Responsible Research Towards Elimination of Malaria in Africa
- 2020 WHO Position Statement: Evaluation of genetically modified mosquitoes for the control of vector-borne diseases
- WHO world malaria report 2020
- WHO Guidance Framework For Testing Genetically Modified Mosquitoes, Second Edition 2021
- Proceedings of an expert workshop on community agreement for gene drive research in Africa – Co-organised by KEMRI, PAMCA and Target Malaria