Matthew S.

CRISPR gene editing promises new therapies but raises concerns about unintended changes. Here, authors present UNCOVERseq, an in-cell method that sensitively detects rare off-target edits, benchmarks performance across editors, and improves risk assessment in therapeutic cells.

Background and ObjectivesNeighborhood disadvantage is a recognized risk factor for Alzheimer disease and Alzheimer disease–related dementias (AD/ADRD) and is linked to AD/ADRD pathology at autopsy. However, there is a lack of large-scale investigations on ...

Clinical outcomes following viral exposures exhibit substantial interindividual variability.

The twolined spittlebug, Prosapia bicincta (TLSB), is an invasive pasture pest on Hawaiʻi Island and causes extensive damage to rangelands.

Siglecs are a family of cell surface receptors generally found on immune cells, which are important in many cellular processes such as cell-adhesion, cell-signaling, and internalization of extracellular particles. While all these smaller functions play a part in...

The Ediacaran Period (635–539 Ma) witnessed the emergence of early animals, rapid oceanic oxygenation, and rising oceanic P availability.

Müller glial cells are the source of retinal regeneration in fish and birds; although this process is efficient in fish, it is less so in birds and...

Common, acute, non-neurotropic respiratory virus infections accelerate ALS disease progression well after the virus has been cleared by augmenting inflammation of glial cells in the spinal cord and motor neuron loss. Anti-inflammatory and antiviral treatment delay disease progression, pointing to infection as a modifiable ALS risk factor.

The brain is a metabolically vulnerable organ as neurons have both high resting metabolic rates and the need for local rapid conversion of carbon s...

Engineered molecular circuits encoded in RNA can act as programmable therapeutics that sense cellular states and elicit precise responses within diseased cells. However, their application depends critically on systems for delivering circuits into cells. Here, we engineer a model delivery system based on the rabies virus that incorporates multiple levels of control over the viral life cycle and cargo. We demonstrate controlled release of viral vectors from sender cells, conditional entry into target cells based on cell-surface proteins, restricted viral replication governed by intracellular protein content, and an escaper-resistant mechanism for viral elimination with drugs. In parallel, we integrate RNA-sensing and protease-controlled circuits to regulate cargo expression and activity at post-transcriptional and post-translational levels. Together, these strategies illustrate how viral and protein engineering can establish multi-level control at both the viral and cargo levels to facilitate specificity in future therapeutic RNA delivery systems.