Respiratory outcomes of onasemnogene abeparvovec treatment for spinal muscular atrophy: national real-world cohort study.

Onasemnogene abeparvovec (OA) is a novel gene replacement therapy for patients with spinal muscular atrophy (SMA). This study provides real-world respiratory data for pediatric SMA patients receiving OA who were assessed before and one year after treatment in a multicenter cohort study conducted from 2019 to 2021. Twenty-five OA-treated SMA patients (23 with type 1 and 2 with type 2; median age at treatment 6.

Genotyping Error Detection and Customised Filtration for SNP Datasets.

A major challenge in analysing single-nucleotide polymorphism (SNP) genotype datasets is detecting and filtering errors that bias analyses and misinterpret ecological and evolutionary processes. Here, we present a comprehensive method to estimate and minimise genotyping error rates (deviations from the 'true' genotype) in any SNP datasets using triplicates (three repeats of the same sample) in a four-step filtration pipeline. The approach involves: (1) SNP filtering by missing data; (2) SNP filtering by error rates; (3) sample filtering by missing data and (4) detection of recaptured individuals by using estimated SNP error rates.

Transcriptome, hormonal, and secondary metabolite changes in leaves of DEFENSE NO DEATH 1 (DND1) silenced potato plants.

DEFENSE NO DEATH 1 (DND1) is a cyclic nucleotide-gated ion channel protein. Earlier, it was shown that the silencing of DND1 in the potato (Solanum tuberosum L.) leads to resistance to late blight, powdery mildew, and gray mold diseases.

Treating late-onset Tay Sachs disease: Brain delivery with a dual trojan horse protein.

Tay-Sachs (TS) disease is a neurodegenerative disease resulting from mutations in the gene encoding the α-subunit (HEXA) of lysosomal β-hexosaminidase A (HexA). We report that (1) recombinant HEXA alone increased HexA activity and decreased GM2 content in human TS glial cells and peripheral mononuclear blood cells; 2) a recombinant chimeric protein composed of HEXA linked to two blood-brain barrier (BBB) entry elements, a transferrin receptor binding sequence and granulocyte-colony stimulating factor, associates with HEXB ; reaches human cultured TS cells lysosomes and mouse brain cells, especially neurons, ; lowers GM2 in cultured human TS cells; lowers whole brain GM2 concentration by approximately 40% within 6 weeks, when injected intravenously (IV) to adult TS-mutant mice mimicking the slow course of late-onset TS; and increases forelimbs grip strength. Hence, a chimeric protein equipped with dual BBB entry elements can transport a large protein such as HEXA to the brain, decrease the accumulation of GM2, and improve muscle strength, thereby providing potential treatment for late-onset TS.