Biology subjects

Carrillo, A.

Publications and source records attributed to Carrillo, A..

3 recordsLinked to original sources

bioRxiv2025

Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease

Huntingtons disease (HD) is an inherited neurodegenerative disorder caused by an expansion of a CAG trinucleotide repeat in the huntingtin (HTT) gene, which leads to a mutant protein that destroys neurons in the brain. Despite intense effort, there remains no approved disease-modifying therapy for HD. Here we develop a pan-HTT-targeting CRISPR-Cas9 system that, when delivered to the striatum of R6/2 and YAC128 mice by AAV5, lowered mutant HTT mRNA and protein by 55-80% via its induction of frameshift-inducing indel mutations in HTT exon 1. Cas9 targeting improved motor coordination and locomotor activity, decreased anxiety-like deficits, reduced clasping and weight loss, limited striatal atrophy, and decreased the formation of intranuclear inclusions immunoreactive for the mutant HTT protein. In Hu21/21 mice, which carry the wild-type human HTT gene in lieu of the mouse ortholog, Cas9 lowered the HTT protein by 44% but induced no measurable behavioral deficits and had no adverse effect on neuronal viability, though its targeting was associated with neuroinflammation. Altogether, our results demonstrate the ability for a newly developed pan-HTT-targeting Cas9 system to affect HD-related phenotypes across models and provides insights into its tolerability.

bioengineering↗

bioRxiv2025

Sub-daily Bermuda Atlantic Time Series virus sampling reveals taxonomy, host, and functional differences at the population, but not community level

Ocean microbes contribute to biogeochemical cycles and ecosystem function, but they do so under top-down pressure imposed by viruses. While viruses are increasingly understood spatially and beginning to be incorporated into predictive modeling, high-frequency ocean virus dynamics remain understudied due to methodological challenges. Here we sampled stratified Bermuda Atlantic Time Series (BATS) waters for 112 hours at sub-daily 4-(surface) or 12-(deep chlorophyll maximum) hour intervals, purified viral particles from these samples, sequenced their metagenomes, and used the resulting data to characterize high-frequency virus community dynamics. Aggregated community diversity metrics changed with depth, but were not statistically significant temporally at a fixed location. However, finer-scale population-level analyses revealed both depth and temporal change, including physicochemical depth-driven differences and, in surface waters, thousands of viral populations that exhibited statistically significant diel rhythms. Statistical analyses revealed three main archetypes of temporal dynamics that themselves differed in abundance patterns, host predictions, viral taxonomy, and gene functions. Among these, highlights include viruses resembling an archetype with a night peaking pattern in activity that include an over-representation of viruses that putatively infect Prochlorococcus, a phototrophic cyanobacteria. Together, these efforts provide baseline community-and population-scale short-time-frame observations relevant to future climate state modeling.

microbiology↗

bioRxiv2024

A fast, muscle-actuated biohybrid swimming robot

The integration of biological actuators with soft scaffolds has led to biohybrid robots including microscale flagellate-like swimmers which generate thrust by waving their flagella-like tails. However, they achieve swimming speeds of only 0.014 body lengths per minute, Reynolds number (Re) [~] 10-3, which is much slower than natural flagellates (O(102 - 103) body lengths per minute). To investigate this, we applied theoretical and experimental methods, including fabrication of a swimmer that converts muscle contractions into large angular tail displacements, reaching swimming speeds of 86.8 m/s (0.58 body lengths per minute), surpassing low-Re predictions. Swimming dynamics sharply transition from a low-Re ([~] 10-3) to an intermediate-Re ([~] 0.1) regime when the actuation angle exceeded 4{degrees}. We used the swimmer to study the ability of muscle to adapt to mechanical stiffness and the beneficial effects of neuromuscular coculture on muscle development. These insights into mechanical and chemical cues will help optimize future biobots. TeaserHow are biological flagellate swimmers like E. coli and sperm cells so fast? We have built a new biohybrid robot to explore the theory.

bioengineering↗