Genetic modification for the control of mosquitoes is frequently touted as a solution for a variety of vector-borne diseases. There has been some success using non-insecticidal methods like sterile or incompatible insect techniques to control arbovirus diseases. However, control by genetic modifications to reduce mosquito populations or create mosquitoes that are refractory to infection with pathogens are less developed. The advent of CRISPR-Cas9-mediated gene drives may advance this mechanism of control. In this review, use and progress of gene drives for vector control, particularly for malaria, is discussed. A brief history of population suppression and replacement gene drives in mosquitoes, rapid advancement of the field over the last decade and how genetic modification fits into the current scope of vector control are described. Mechanisms of alternative vector control by genetic modification to modulate mosquitoes' immune responses and anti-parasite effector molecules as part of a combinational strategy to combat malaria are considered. Finally, the limitations and ethics of using gene drives for mosquito control are discussed.
Persistence of human immunodeficiency virus (HIV) reservoirs prevents viral eradication, and consequently HIV-infected patients require lifetime treatment with antiretroviral therapy (ART) [1-5]. Currently, there are no effective therapeutics to prevent HIV rebound upon ART cessation. Here we describe an HIV/SIV Rev-dependent lentiviral particle that can be administered to inhibit viral rebound [6-9]. Using simian immunodeficiency virus (SIV)-infected rhesus macaques as a model, we demonstrate that the administration of pre-assembled SIV Rev-dependent lentiviral particles into SIVmac239-infected Indian rhesus macaques can lead to reduction of viral rebound upon ART termination. One of the injected animals, KC50, controlled plasma and CNS viremia to an undetectable level most of the time for over two years after ART termination. Surprisingly, detailed molecular and immunological characterization revealed that viremia control was concomitant with the induction of neutralizing antibodies (nAbs) following the administration of the Rev-dependent vectors. This study emphasizes the importance of neutralizing antibodies (nAbs) for viremia control [10-15], and also provides proof of concept that the Rev-dependent vector can be used to target viral reservoirs, including the CNS reservoirs, in vivo. However, future large-scale in vivo studies are needed to understand the potential mechanisms of viremia control induced by the Rev-dependent vector.
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