Researchers assessed the impact of gene amplification on cross-species adaptation.
BigField GEG Tech's insight:
In a recent study published on the bioRxiv preprint server, researchers evaluated the impact of gene amplification on cross-species adaptation. The researchers demonstrated that the impact of RhTRS1 gene amplification could effectively rescue viral replication in fibroblasts from partially resistant African green monkeys (AGMs). The team infected A549 cells with vaccinia virus (VACV) + RhTRS1 or the VACV strain named Copenhagen, expressing a beta-galactosidase (bg) reporter gene. The team explored whether amplification of rhtrs1 could increase the extent of viral replication in the absence of PKR. The team also infected RNase L competent A549 cells or regularly spaced short palindromic repeats with CRISPR in clusters of RNase L deletion present in existing A549 cells with VACV-RhTRS1, VACV-bg or AGM-A. The results of the study showed that A549 cells restricted VACV + RhTRS1 replication by nearly 10,000-fold compared to VACV-bg replication. The team noted that deletion of A549 PKR cells enhanced VACV + RhTRS1 replication by up to 1000-fold compared to PKR-competent cells. The team observed that RNAase L had no impact on VACV-bg replication.
A breakthrough study, led by researchers from the University of California, Irvine, results in the restoration of retinal and visual functions of mice models suffering from inherited retinal disease.
BigField GEG Tech's insight:
The new generation CRISPR technology allows the restoration of the retinal and visual function after gene therapy in the treatment of a wide range of inherited ocular diseases. Using a mouse model with Leber Congenital Amaurosis (LCA) due to a clinically relevant pathogenic mutation in the Rpe65 gene, the team from the University of California at Irvine has successfully demonstrated the therapeutic potential of base editing for the treatment of LCA and by extension other blinding hereditary diseases. The researchers overcame some of the obstacles to the CRISPR-Cas9 system, such as unpredictable off-target mutations and low editing efficiency, by using cytosine and adenine base editors. The use of these editors allowed them to correct point mutations in a precise and predictable manner while minimizing unintentional mutations that could cause undesirable side effects. The basic editing treatment restored retinal and visual function in LCA mice to near normal levels. These results are extremely encouraging and represent a major step forward in the development of treatments for inherited retinal diseases.
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In a recent study published on the bioRxiv preprint server, researchers evaluated the impact of gene amplification on cross-species adaptation. The researchers demonstrated that the impact of RhTRS1 gene amplification could effectively rescue viral replication in fibroblasts from partially resistant African green monkeys (AGMs). The team infected A549 cells with vaccinia virus (VACV) + RhTRS1 or the VACV strain named Copenhagen, expressing a beta-galactosidase (bg) reporter gene. The team explored whether amplification of rhtrs1 could increase the extent of viral replication in the absence of PKR. The team also infected RNase L competent A549 cells or regularly spaced short palindromic repeats with CRISPR in clusters of RNase L deletion present in existing A549 cells with VACV-RhTRS1, VACV-bg or AGM-A. The results of the study showed that A549 cells restricted VACV + RhTRS1 replication by nearly 10,000-fold compared to VACV-bg replication. The team noted that deletion of A549 PKR cells enhanced VACV + RhTRS1 replication by up to 1000-fold compared to PKR-competent cells. The team observed that RNAase L had no impact on VACV-bg replication.