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Adeno-associated virus (AAV) has found immense success as a delivery system for gene therapy, yet the small 4.7 kb packaging capacity of the AAV sharply limits the scope of its application. In addition, high doses of AAV are frequently required to facilitate therapeutic effects, leading to acute toxicity issues. While dual and triple AAV approaches have been developed to mitigate the packaging capacity problem, these necessitate even higher doses to ensure that co-infection occurs at sufficient frequency. To address these challenges, we herein describe a novel delivery system consisting of adenovirus (Ad) covalently linked to multiple adeno-associated virus (AAV) capsids as a new way of more efficiently co-infecting cells with lower overall amounts of AAVs. We utilize the DogTag-DogCatcher (DgT-DgC) molecular glue system to construct our AdAAVs and we demonstrate that these hybrid virus complexes achieve enhanced co-transduction of cultured cells. This technology may eventually broaden the utility of AAV gene delivery by providing an alternative to dual or triple AAV which can be employed at lower dose while reaching higher co-transduction efficiency.

Although adeno-associated virus (AAV) gene therapy has shown enormous promise and led to five clinically approved treatments,1–3 it is consistently hampered by the vector’s low DNA packaging capacity of 4.7 kb. Great effort has gone into developing dual AAV systems, which deliver two parts of a therapeutic gene in separate capsids that aim to co-infect the same cells.4–7 Analogous triple AAV systems have also been explored.8,9 Dual and triple AAV systems can recombine their split genes into complete form through mechanisms of DNA trans-splicing, RNA trans-splicing, or protein splicing via split inteins.5,7 However, dual and triple AAVs typically require higher doses to achieve efficient co-transduction of cells, especially when systemic administration is necessary.10 This makes sense since the likelihood of two or three cargos reaching the same cell should roughly correspond to the proportion of a single cargo reaching the cell squared or cubed respectively.

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What did NASA’s Double Asteroid Redirection Test (DART) spacecraft on the asteroid moon, Dimorphos, teach astronomers about altering the trajectory of asteroids and asteroids’ formation and evolution? This is what a recent study published in The Planetary Science Journal hopes to address as an international team of researchers investigated the potential geological changes made to Dimorphos, which orbits its parent asteroid, Didymos, when DART impacted the former in September 2022. This study holds the potential to help scientists better understand the formation and evolution of asteroids throughout, and potentially beyond, the solar system, which could hold implications for the early history of the solar system, as well.

“For the most part, our original pre-impact predictions about how DART would change the way Didymos and its moon move in space were correct,” said Dr. Derek Richardson, who is a professor of astronomy at the University of Maryland, a DART investigation working group lead, and lead author on the study. “But there are some unexpected findings that help provide a better picture of how asteroids and other small bodies form and evolve over time.”

For the study, the researchers analyzed post-impact data of the DART spacecraft on Dimorphos based on predictions made prior to the impact, which could help in planning for the European Space Agency’s upcoming Hera spacecraft mission to Didymos, which is slated to launch in October 2024 and arrive at Didymos in December 2026. In the end, the researchers found that along with Dimorphos’ orbital parameters being influenced by the impact, its physical shape was altered, as well. This resulted in the small asteroid moon becoming elongated towards its poles, whereas its poles were squished prior to impact. This indicates varying formation and evolutionary processes regarding its geologic composition.

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Scientists may have found a new way to unlock the vast secrets of the Big Bang—the cosmic event thought to have kicked off the expansion of the universe billions of years ago. The revelation came in 2023, when scientists found nearly imperceptible ripples within the very fabric of space and time as we know it.

The ripples appear to be associated directly with rapidly spinning neutrons that we call pulsar timing arrays. Researchers believe that studying gravitational waves—more specifically, the low-frequency background hum they emit—may allow us to learn more about the Big Bang and the universe’s very beginning.

For a long time, researchers have believed that the low-frequency background hum of gravitational waves in our universe was part of a “phase transition” that occurred just after the Big Bang. However, a new bit of research could further unlock the secrets of the Big Bang and suggests that this might not be the case at all.

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Organoid intelligence (OI) is an emerging scientific field aiming to create biocomputers where lab-grown brain organoids serve as ‘biological hardware’

In their article, published in Frontiers in Science, Smirnova et al., outline the multidisciplinary strategy needed to pursue this vision: from next-generation organoid and brain-computer interface technologies, to new machine-learning algorithms and big data infrastructures.

https://www.frontiersin.org/journals/.…

Citation:

Continue reading “Organoid intelligence: a new biocomputing frontier | Frontiers in Science” | >

A new Nature Human Behaviour study, jointly led by Dr. Margherita Malanchini at Queen Mary University of London and Dr. Andrea Allegrini at University College London, has revealed that non-cognitive skills, such as motivation and self-regulation, are as important as intelligence in determining academic success. These skills become increasingly influential throughout a child’s education, with genetic factors playing a significant role.

The research, conducted in collaboration with an international team of experts, suggests that fostering non-cognitive skills alongside could significantly improve educational outcomes.

“Our research challenges the long-held assumption that intelligence is the primary driver of ,” says Dr. Malanchini, Senior Lecturer in Psychology at Queen Mary University of London.

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