Articles in 2018

Informing physicians who prescribe opioids about opioid-linked deaths in their practice reduces future opioid prescribing.

Acquired resistance to CD19-targeted CAR T cell therapy can occur through mutations in the CD19 gene or after insertion of a chimeric antigen receptor (CAR) into leukemia cells, resulting in the adjacent receptor being masked by the CAR.

Thanks to improvements in data collection and analysis, some polygenic risk scores that predict disease risk are approaching the same predictive accuracy offered by tests for monogenic mutations. The time to think about how best to incorporate polygenic tests in the clinic is now.

Will the rise of patient navigators help avert health disparities?

Base editors function in mouse fetuses and in the livers of adult mice to treat a genetic disorder.

Virologists say sewage systems are flush with opportunity.

AAV-mediated base editing corrects an autosomal recessive mutation in the Pah^enu2 gene and ameliorates molecular deficits in a mouse model of metabolic liver disease.

Targeting different aspects of mutant CFTR structural defects with combination therapy leads to more potent rescue of function than that following single therapy.

A biocompatible device built from naturally dissolving components and controlled by wireless technology enables programmable electrical stimulation of injured rodent peripheral nerves to accelerate regeneration and recovery.

Viral-mediated base editing in utero enables therapeutic editing of two metabolic genes in mice.

Systemic administration of human PBGD mRNA encapsulated in lipid nanoparticles ameliorates disease phenotypes in mouse and rabbit models of acute hepatic porphyria and is safe in nonhuman primates.

Neoadjuvant combination treatment with nivolumab and ipilimumab in patients with high-risk melanoma results in higher response rates than nivolumab monotherapy and warrants future optimization of dosing regimens to preserve efficacy while limiting toxicity.

The long-term follow-up results of a phase 1/2 retinal gene therapy clinical trial for choroideremia (NCT01461213) support the safety and efficacy of the treatment.

Large tumors induce anemia and expansion of CD45⁺ immature erythroid cells, which represent a major immunosuppressive population in the spleen, contributing to systemic suppression of T cell immunity in late-stage cancer.

Neoadjuvant combination immunotherapy in patients with advanced melanoma shows favorable activity over adjuvant treatment and warrants future evaluation with modified dosing schedules to reduce treatment-related adverse events.

Mutations in the CD19 gene suggesting irreversible loss of its surface expression are identified in the majority of analyzed cases of CD19^– relapse in two clinical trials of pediatric ALL CD19 CAR T therapy, offering considerations for the rational choice of follow-up therapies.