Adeno-Associated Virus Gene Therapy Development: Early Planning and Regulatory Considerations to Advance the Platform Vector Gene Therapy Program.

Gene therapy development presents multiple challenges, and early planning is vital in the successful implementation of such programs. The Platform Vector Gene Therapy (PaVe-GT) program is a National Institutes of Health (NIH) initiative developing adeno-associated virus (AAV) gene therapies for four low-prevalence rare diseases. Utilizing the platform-based approach, the program aims to incorporate efficiencies throughout the preclinical and clinical development processes followed by public dissemination of scientific and regulatory learnings.

The genetics of TDP43-Type-C neurodegeneration: a whole genome sequencing study.

Frontotemporal lobar degeneration-TDP Type C (TDP-C) is a unique neurodegenerative disease that starts by attacking the anterior temporal lobe leading to language and/or behavioral syndromes. Current literature on the genetic associations of TDP-C, which we have reviewed here, is uneven and lacks a discernible corpus of robust findings. In our study, we completed genome wide hypothesis-free analyses utilizing artificial Intelligence (AI) to identify rare and common variants associated with TDP-C.

Differential Packing of CsMoBr Cluster-Based Halide in Variable Diameter Carbon Nanotubes with Elimination and Polymerization to 1D [MoBr] Ising Model Structures by Steric Confinement.

We present detailed findings on the imaging, structure, and vibrational properties of novel hybrids of the red-emitting octahedral cluster-based compound CsMoBr encapsulated within single-walled carbon nanotubes (SWCNTs) of varying diameter. We explore the subtle relationship between the SWCNT internal diameter and CsMoBr cluster packing and find a hierarchical relationship between the nature of the cluster packing and a progressive tendency toward formation of one-dimensional (1D) structures as the SWCNT diameter narrows from 24 to 11 Å. As the internal SWCNT van der Waals radius approaches the outside diameter (OD) of the [{MoBr}Br] (more simplistically, [MoBr]) molecular anion species, SWCNT steric confinement causes a compositional elimination and polymerization resulting in the formation of reduced extended [MoBr] nanoribbons which approximate 1D Ising model structures.

Breath biopsy in inborn errors of metabolism: A proof-of-principle study in propionic acidemia.

Background: Impaired oxidation of branched chain amino acids may give rise to volatile organic compounds (VOCs). We hypothesized that VOCs will be present in exhaled breath of participants with propionic acidemia (PA), and their relative abundance would correlate with clinical and biochemical characteristics of the disease.

Methods: We enrolled 5 affected participants from a natural history study of PA (ClinicalTrials.