Risk Assessment for Controlling Mosquito Vectors with Engineered Nucleases, Part I: Sterile Male Construct Final report

[摘要] In February 2014 CSIRO was engaged by the Foundation for the National Institutes of Health (FNIH) to conduct a risk assessment of a proposal to control mosquito vectors of malaria by genetic engineering with the I-PpoI Homing Endonuclease Gene (HEG). The CSIRO risk assessment focuses on an accidental escape of G3 strain mosquitoes and mosquitoes modified with the I-PpoI construct from three African insectaries. Following a detailed literature review and a systematic, inductive hazard analysis, the project team in conjunction with members of the HEG consortium identified 5 assessment endpoints:1. increase in the vectorial capacity of genetically modified mosquitoes2. transmission of a novel (i.e. not previously known to be vectored by An. gambiae) blood borne pathogen to human or vertebrate host3. spread of the I-PpoI construct in non-target eukaryotes4. spread of the I-PpoI construct in non-eukaryotes5. spread of the I-PpoI construct in the An. gambiae complexThese endpoints together with the decisions regarding hazards that the CSIRO risk team were asked not to address, namely hazards associated with project failure, allergic and/or toxic responses and the potential incidental impacts associated with spraying in the event of a catastrophic loss, determine the current scope of the risk assessment.The risk assessment quantified the risk associated with these endpoints by using direct elicitation with domain experts to develop subjective prior probability distributions for key malaria transmission parameters, and basic events within fault trees. The elicitation was performed with16 independent (of the HEG consortium) experts, and with 8 members of the consortium. In total 1116 subjective probability density functions and 70 constants were retained for subsequent analysis, together with 1588 comments, covering 393 and 544 basic events (and vectoral capacity parameters) respectively.The risk assessment adopted a conservative approach by assuming a catastrophic loss of 10,000 mosquitoes from the African insectaries. The results of the fault tree analysis (Table 8.1) indicate that the median value of the risk of G3 strain mosquitoes transmitting a novel blood based pathogen, or I-PopI modified mosquitoes spreading the construct to non-target eukaryotes or non-eukaryotes is negligible (6.4e-07 to 2.0e-11). The 90th percentile of these risks varies from very low to negligible (7.9e-04 to 1.2e-07).Comments provided by the experts during the elicitation also suggest that the risk of I-PopI mosquitoes transmitting a novel blood-based pathogen would probably be lower than G3 mosquitoes, whilst the risk of the I-PopI construct spreading to non-target eukaryotes and non-eukaryotes would not be materially different if it were deployed in a self-sustaining “Y-Drive” system.The median value of the risk of the construct spreading in An. coluzzi or An. arabiensis was estimated to be extremely low (7.0e-06), whilst the median value of the risk of the construct spreading in An. gambiae was estimated to be low (1.5e-03). The median value for the An. coluzzi or An. arabiensis risk, however, is sensitive to the analysis method used in the fault tree, and this rises to low (1.1e-03) under an alternative strategy. The 90th percentile of these risks varies from low to moderate (1.2e-02 to 2.7e-01).The assessment of risk of an increase in vectorial capacity was also based on a direct elicitation of parameters that are widely accepted to be the most relevant in this context. If we make the reasonable assumption of strong positive dependence between strains, then the estimated probability of an increase in a transmission risk index of escaped G3 mosquitoes and I-PopI mosquitoes, relative to wild type, is 7e-03 and 5.2e-02 respectively.The risk assessment concluded by examining the ability of different monitoring designs to detect mosquitoes outside of a generic insectary, for range of escape scenarios (trickle to catastrophic loss).

[发布日期] 2015-07-31 [发布机构] CSIRO

[学科分类] 地球科学(综合)