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Mosquito transgenesis for malaria control

2021; Elsevier BV; Volume: 38; Issue: 1 Linguagem: Inglês

10.1016/j.pt.2021.08.001

1471-5007

Shengzhang Dong, Yuemei Dong, Maria L. Simões, George Dimopoulos,

Invertebrate Immune Response Mechanisms

Mosquito transgenesis has advanced rapidly in recent years and emerged as an attractive tool for controlling malaria. Genetically engineered parasite-refractory mosquitoes efficiently suppress malaria parasite infection and transmission in laboratory conditions. Numerous antiparasite effector and parasite host factor genes can potentially be used to generate genetically engineered (GE) mosquitoes. Gene drives make the implementation of GE mosquitoes to control malaria both affordable and sustainable. Several technical issues and public concerns need to be addressed before actual application of GE mosquitoes for malaria control. Malaria is one of the deadliest diseases. Because of the ineffectiveness of current malaria-control methods, several novel mosquito vector-based control strategies have been proposed to supplement existing control strategies. Mosquito transgenesis and gene drive have emerged as promising tools for preventing the spread of malaria by either suppressing mosquito populations by self-destructing mosquitoes or replacing mosquito populations with disease-refractory populations. Here we review the development of mosquito transgenesis and its application for malaria control, highlighting the transgenic expression of antiparasitic effector genes, inactivation of host factor genes, and manipulation of miRNAs and lncRNAs. Overall, from a malaria-control perspective, mosquito transgenesis is not envisioned as a stand-alone approach; rather, its use is proposed as a complement to existing vector-control strategies. Malaria is one of the deadliest diseases. Because of the ineffectiveness of current malaria-control methods, several novel mosquito vector-based control strategies have been proposed to supplement existing control strategies. Mosquito transgenesis and gene drive have emerged as promising tools for preventing the spread of malaria by either suppressing mosquito populations by self-destructing mosquitoes or replacing mosquito populations with disease-refractory populations. Here we review the development of mosquito transgenesis and its application for malaria control, highlighting the transgenic expression of antiparasitic effector genes, inactivation of host factor genes, and manipulation of miRNAs and lncRNAs. Overall, from a malaria-control perspective, mosquito transgenesis is not envisioned as a stand-alone approach; rather, its use is proposed as a complement to existing vector-control strategies. peptides or genes with the ability to inhibit malaria parasite infection in their vertebrate hosts or mosquito vectors, including exogenous antiparasite peptides and endogenous mosquito immune genes such as antimicrobial peptide genes. clustered regularly interspaced short palindromic repeats/CRISPR-associated sequence 9, a genome-editing tool comprising a nuclease (Cas9) and a guide RNA that directs the nuclease to bind to specific genomic loci and introduce double-stranded breaks (DSBs) to disrupt a target gene. a measure of the sum of years of the health loss due to premature death and years of nonfatal disease burden due to disability. reduction in fitness associated with carrying foreign DNA or introducing a mutation into the DNA. Several parameters are used to evaluate fitness cost in GE mosquitoes, including larval and pupal development, longevity, body size, reproduction, and blood-feeding capability. an in vitro engineered DNA fragment that includes a target gene, promoters, fluorescent markers, and other essential DNA sequences for generating GE mosquitoes. a selfish gene that spreads through a population by expressing an endonuclease that creates a double-stranded break in a DNA sequence and then copies itself to this site. an important mechanism for the repair of complex DNA damage, such as DNA double-stranded breaks; it uses long homologous sequences surrounding DSBs to incorporate new DNA fragments. a mosquito gene that facilitates infection of the mosquito with a pathogen. the integration of exogenous DNA into the mosquito genome through germline transformation so that it is stably inherited as a transgene in subsequent generations. Broadly, transgenesis includes the inactivation of a gene(s) in the genome through germline mutation. The main goal is to interrupt pathogen transmission through the introduction of DNA fragments or inactivation of a gene(s) in the mosquito genome. replacing the local mosquito population with a population of disease-refractory mosquitoes, thereby reducing disease transmission but not eliminating the species in the local ecological niche and thus limiting the risk of secondary insect-pest emergence. reducing the local mosquito population by introducing genetically engineered mosquitoes that are lethal or sterile, to a level that will block disease transmission. single-chain fragment variable (scFv), the smallest fragment of an antibody with the same antigen-binding specificity. It is generated by the fusion of the variable heavy and light chains of a monoclonal antibody (mAb) through a short polypeptide linker. mobile DNA sequences with terminal inverted repeats that encode a transposase enzyme that catalyzes excision and random insertion of sequences into the genome. the ability of a mosquito to transmit a disease. It normally involves the capacity of a mosquito to be infected by a pathogen and then to transmit the pathogen through its bite.