The way cancer-causing proteins accumulate in tumours may influence how effectively a promising new generation of medicines can remove them, a study suggests.
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Alzheimer’s Damage in Mice Reversed With Just Two Injections
Slowing the progression of Alzheimer’s disease is the goal of most existing treatments, but reversing it is much harder. That’s because once neurons are lost, the adult brain lacks the ability to replace them.
But new research, led by scientists at the University of South Carolina, has shown promise in regrowing neurons in brain organoids, and restoring cognition in mouse models of Alzheimer’s.
“After just two injections, these mice became smarter,” says Peisheng Xu, professor of pharmaceutics at the University of South Carolina and corresponding author of the new study, published in the journal Cell Biomaterials.
Nanoparticles regenerate neurons and improve cognition in Alzheimer’s mice
The adult human brain has limited capacity to repair or regenerate neurons lost to Alzheimer’s disease, the most common type of dementia. Existing treatments can slow disease progression but do not reverse cognitive decline. In a study publishing in the Cell Press journal Cell Biomaterials on August 26, researchers show that engineered nanoparticles can not only regenerate neurons in human brain organoids but also restore neural circuits and improve cognition in mice.
The new neurons can become mature and survive. We also confirmed much higher neuron density in the brains of treated mice.
Cell factories that manufacture microvesicles containing gene silencing RNA prodrugs
Precise and reversible suppression of gene expression by antisense RNA sequences is a strategy that is widely used in both basic research and clinical medicine (for reviews, see 1–3). Naked or unmodified antisense RNA is rapidly degraded in biological fluids and is inefficiently internalized by cells (4, 5). Consequently, antisense RNAs used to silence gene expression have been delivered by encapsulating them extracellularly in lipid-based or gold-based nanoparticles (6, 7) or in vesicles released from cells grown in culture (8–11). However, consistent and quantitatively reproducible RNA encapsulation in particles formed extracellularly has been a challenge (12, 13).
Arrestin domain–containing 1 (ARRDC1)-mediated microvesicles (ARMMs) are a naturally occurring distinct subclass of extracellular vesicles (EVs) that are uniquely dependent on the production of the arrestin-like cellular protein ARRDC1, and which—unlike other vesicles released from cells—are formed by outward budding of cytoplasmic membranes (14). During ARMMs formation, the ARRDC1 protein is attached to ARMMs membranes and is loaded into ARMMs—carrying along other macromolecules linked to it (14, 15). ARMMs can fuse with the plasma membranes of cells they encounter, and ARMMs cargos are discharged directly into the cytosol of recipient cells instead of being internalized by endocytosis—thus avoiding degradative actions of endosomal enzymes (14, 15). Collectively, these properties have prompted investigation of ARMMs’ abilities to deliver biologically manufactured macromolecules intercellularly (15–17).
Here, we describe and test a platform that synthesizes short hairpin RNA (shRNA) prodrugs as biochemically inert modules that are protected from RNA processing and degradation during their production and loading into ARMMs, but which become active gene-silencing agents upon delivery to recipient cells.
The Turtle in Your Bloodstream
This week on Heliox, we trace the science from a rigorous long COVID symptom meta-analysis, through the structural biology of the “turtle” variant, to why a proven diagnostic test still isn’t in your local lab — and why clean air might be the fastest fix we actually have.
Podcast Episode · Heliox: Where Evidence Meets Empathy 🇨🇦 · September 2 · 17m.
Scientists may have detected the 1st direct evidence of dark matter
As LUX-ZEPPLIN continues to gather the largest dataset in dark matter science, the team will determine if this event has grown in significance or if its significance fades.
One definite positive is the fact that WIMP/ matter interactions are so rare that it wouldn’t take many detections such as this to confirm the existence of WIMP dark matter, thus solving the puzzle of what the universe’s most mysterious stuff actually is composed of.
“We expect dark matter events to be extremely rare, so only a handful could mark the first detection of WIMP dark matter,” Eriksen said.
