Using CRISPR/Cas9, a gene editing tool gene, the FREP1 gene can be inactivated to reduce mosquitoes vulnerability to Plasmodium parasite, a genus that causes malaria in humans. The findings of this study are published in the Journal of PLOS Pathogens.
Inside an Anopheles gambiae (A. gambiae) mosquito, Plasmodium undergoes a series of infection steps before reaching the mosquito's salivary gland, from which it spreads to bitten humans. This infection cycle relies on the activity of several mosquito proteins. Recently developed CRISPR-Cas9 tools offer new opportunities to study these proteins and determine whether they can be targeted to block malaria transmission.
Gene-Editing Tool - CRISPR/Cas9 Made More User-Friendly by Indian-American Researchers
CRISPR/Cas9 is a tool that can target a particular segment of DNA in cells, such as a gene mutation, and replace it with a genetic sequence.
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‘Using CRISPR/Cas9 the ability of the malarial parasite to infect mosquitoes can be reduced and by this malarial transmission to vulnerable humans can be prevented.’
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Dimopoulos group had previously identified and examined several mosquito proteins involved in Plasmodium infection, including fibrinogen-related protein 1 (FREP1). A vaccine candidate based on targeting FREP1 was recently developed, but Dimopoulos' group took a different approach. They used a CRISPR/Cas9 technique to inactivate the FREP1 gene in A. gambiae mosquitos and explore the effects on malaria parasite infection.
The team found that FREP1 inactivation via CRISPR/Cas9 significantly suppressed infection of the mosquitoes with both human and rodent Plasmodium parasites. This supports potential for CRISPR/Cas9 technology in altering the genomes of wild mosquito populations to prevent the spread of malaria, which kills nearly 500,000 people worldwide every year.
![New Insights into Tumor-Infiltrating T Cells may Pave the Way for Precision Medicine]( "New Insights into Tumor-Infiltrating T Cells may Pave the Way for Precision Medicine")
A distinct gene module for T cell dysfunction distinct from activation in tumor-infiltrating T cells has been identified by investigators.
However, the permanent inactivation of FREP1 in all mosquito stages and tissues also resulted in fitness costs for the mosquitoes, including reduced blood-feeding ability, lower fertility, a lower egg hatching rate, slowed development, and reduced longevity after feeding on blood. This raises concerns that mosquitoes with permanently inactivated FREP1 would not be able to compete with non-mutant mosquitoes in the wild effectively enough to block malaria transmission. The investigators are now exploring ways to inactivate FREP1 in the gut of adult female mosquitoes only, with the hope to reduce the fitness cost while retaining resistance to the malaria parasite.
Nonetheless, the findings highlight the potential for CRISPR/Cas9 gene editing techniques to inactivate parasite-host factors and improve understanding of malaria. Further research could also explore strategies to enable mosquitoes with inactivated FREP1 to successfully compete with non-mutants.
Source: Eurekalert
New Insights into Tumor-Infiltrating T Cells may Pave the Way for Precision Medicine
A distinct gene module for T cell dysfunction distinct from activation in tumor-infiltrating T cells has been identified by investigators.
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However, the permanent inactivation of FREP1 in all mosquito stages and tissues also resulted in fitness costs for the mosquitoes, including reduced blood-feeding ability, lower fertility, a lower egg hatching rate, slowed development, and reduced longevity after feeding on blood. This raises concerns that mosquitoes with permanently inactivated FREP1 would not be able to compete with non-mutant mosquitoes in the wild effectively enough to block malaria transmission. The investigators are now exploring ways to inactivate FREP1 in the gut of adult female mosquitoes only, with the hope to reduce the fitness cost while retaining resistance to the malaria parasite.
Nonetheless, the findings highlight the potential for CRISPR/Cas9 gene editing techniques to inactivate parasite-host factors and improve understanding of malaria. Further research could also explore strategies to enable mosquitoes with inactivated FREP1 to successfully compete with non-mutants.
Source: Eurekalert
Gene Editing Technique Offers Precised Blindness Therapy by Repairing Stem Cells
CRISPR/Cas9 has been heralded as a major breakthrough in genetic engineering to precisely make specific alterations to the DNA in cells and experimental animals.
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 RNA-Based Drugs Give More Control Over Gene Editing ActivityNow, researchers have demonstrated a commercially feasible way to use RNA to turn the CRISPR-Cas9 system on and off as desired - permanently editing a gene. | Advertisement
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