Enhanced sensitivity of neutralizing antibody detection for different AAV serotypes using HeLa cells with overexpressed AAVR.

A cell-based transduction inhibition assay (TI) is widely used in clinical trials to detect neutralizing antibody (NAb) titers against recombinant adeno-associated virus (rAAV), one of the most important criteria to exclude patients in gene therapy. Different cell lines are used in cell-based TI because the rAAV transduction efficiencies vary largely among serotypes. A cell line suitable for TI for most serotypes is highly desirable, especially for those with very low transduction efficiencies such as rAAV8 and rAAV9.

Ferroptosis promotes T-cell activation-induced neurodegeneration in multiple sclerosis.

While many drugs are effective at reducing the relapse frequency of multiple sclerosis (MS), there is an unmet need for treatments that slow neurodegeneration resulting from secondary disease progression. The mechanism of neurodegeneration in MS has not yet been established. Here, we discovered a potential pathogenetic role of ferroptosis, an iron-dependent regulated cell death mechanism, in MS.

Erratum: Long-Term Metabolic Correction of Phenylketonuria by AAV-Delivered Phenylalanine Amino Lyase.

[This corrects the article DOI: 10.1016/j.omtm.

Thrombin induces ACSL4-dependent ferroptosis during cerebral ischemia/reperfusion.

Ischemic stroke represents a significant danger to human beings, especially the elderly. Interventions are only available to remove the clot, and the mechanism of neuronal death during ischemic stroke is still in debate. Ferroptosis is increasingly appreciated as a mechanism of cell death after ischemia in various organs.

Optimization of miR-22 expression cassette for rAAV delivery on diabetes.

MicroRNA-22 (miR-22) was suggested to be important for type 2 diabetes but its functions for this disease remained unclear. Recombinant adeno-associated virus (rAAV)-mediated miR delivery is a powerful approach to study miR functions in vivo, however, the overexpression of miR-22 by rAAV remains challenging because it is one of the most abundant miRs in the liver. In this study, a series of expression cassettes were designed and compared.

Long-Term Metabolic Correction of Phenylketonuria by AAV-Delivered Phenylalanine Amino Lyase.

Phenylketonuria (PKU) is an inherited metabolic disorder caused by mutation within phenylalanine hydroxylase (PAH) gene. Loss-of-function of PAH leads to accumulation of phenylalanine in the blood/body of an untreated patient, which damages the developing brain, causing severe mental retardation. Current gene therapy strategies based on adeno-associated vector (AAV) delivery of PAH gene were effective in male animals but had little long-term effects on blood hyperphenylalaninemia in females.

Long-Term Correction of Copper Metabolism in Wilson's Disease Mice with AAV8 Vector Delivering Truncated ATP7B.

Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism caused by mutations in the gene encoding a liver active copper transport enzyme. Gene therapy with adeno-associated virus (AAV) carrying full-length ATP7B, which is about 4.4 kb, was shown to rescue copper metabolism disorder in WD mouse model.

Association Between PIP4K2A Polymorphisms and Acute Lymphoblastic Leukemia Susceptibility.

Acute lymphoblastic leukemia (ALL) is one of the most common pediatric cancers in the world. Several single-nucleotide polymorphisms (SNPs) locating at PIP4K2A locus were identified to be associated with ALL susceptibility through genome-wide association studies, however, followed by inconsistent reports in replication studies. In this study, we conducted a meta-analysis to investigate the association status of the top independent SNPs (rs7088318 and rs4748793) with ALL susceptibility by combining the data from 6 independent studies, totally including 3508 cases and 12,446 controls with multiethnic populations.