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1. Engineering viral vectors for acoustically targeted gene delivery

   https://doi.org/10.1038/s41467-024-48974-y  

   Li, Hongyi_R; Harb, Manwal; Heath, John_E; Trippett, James_S; Shapiro, Mikhail_G; Szablowski, Jerzy_O (June 2024, Nature Communications)

   Abstract Targeted gene delivery to the brain is a critical tool for neuroscience research and has significant potential to treat human disease. However, the site-specific delivery of common gene vectors such as adeno-associated viruses (AAVs) is typically performed via invasive injections, which limit its applicable scope of research and clinical applications. Alternatively, focused ultrasound blood-brain-barrier opening (FUS-BBBO), performed noninvasively, enables the site-specific entry of AAVs into the brain from systemic circulation. However, when used in conjunction with natural AAV serotypes, this approach has limited transduction efficiency and results in substantial undesirable transduction of peripheral organs. Here, we use high throughput in vivo selection to engineer new AAV vectors specifically designed for local neuronal transduction at the site of FUS-BBBO. The resulting vectors substantially enhance ultrasound-targeted gene delivery and neuronal tropism while reducing peripheral transduction, providing a more than ten-fold improvement in targeting specificity in two tested mouse strains. In addition to enhancing the only known approach to noninvasively target gene delivery to specific brain regions, these results establish the ability of AAV vectors to be evolved for specific physical delivery mechanisms. 

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2. EFFECTS OF OSMOLARITY ON ULTRASOUND-INDUCED MEMBRANE DEPOLARIZATION IN ISOLATED CRAYFISH MOTOR AXON

   TAGEDPFEIYUAN YU, * WOLFGANG (May 2022, Ultrasound in medicine biology)

   Abstract—We have previously identified a novel non-selective membrane conductance (gUS) opened by focused ultrasound (FUS) in crayfish motor axons. In the work described here, we studied gUS properties further by comparing FUS-evoked depolarization (FUSD) in control and hypotonic saline with 75% of control osmolarity. The FUS was a train of 20 FUS bursts (2.1 MHz and 50 ms per burst) delivered at 1 kHz. The amplitude, onset latency, frequency of occurrence and duration of FUSD were compared in a 15-min time window before and after switching to hypotonic saline. Significant increases were observed for amplitude (p < 0.001) and frequency of occurrence (p < 0.01) while the onset latency exhibited a significant decrease (p < 0.001). FUSD duration did not significantly differ. These results support predictions based on our hypothesis that gUS is mediated by opening of nanopores in the lipid bilayer and that stretching of axonal membrane caused by swelling at low osmolarity should increase the probability of nanopore formation under FUS. The FUSD parameters, in addition, exhibited time-dependent trends when the window of observation was expanded to 45 min in each saline. The statistical significance of amplitude and duration differed between 15- and 45-min time windows, indicating the presence of adaptive responses of axonal membrane to osmotic manipulation. (E-mail: jenweilin@bu.edu) © 2022 Published by Elsevier Inc. on behalf of World Federation for Ultrasound in Medicine & Biology. 

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3. Tuning shape and internal structure of protein droplets via biopolymer filaments

   https://doi.org/10.1039/C9SM02462J  

   Scheff, Danielle R.; Weirich, Kimberly L.; Dasbiswas, Kinjal; Patel, Avinash; Vaikuntanathan, Suriyanarayanan; Gardel, Margaret L. (June 2020, Soft Matter)

   Macromolecules can phase separate to form liquid condensates, which are emerging as critical compartments in fields as diverse as intracellular organization and soft materials design. A myriad of macromolecules, including the protein FUS, form condensates which behave as isotropic liquids. Here, we investigate the influence of filament dopants on the material properties of protein liquids. We find that the short, biopolymer filaments of actin spontaneously partition into FUS droplets to form composite liquid droplets. As the concentration of the filament dopants increases, the coalescence time decreases, indicating that the dopants control viscosity relative to surface tension. The droplet shape is tunable and ranges from spherical to tactoid as the filament length or concentration is increased. We find that the tactoids are well described by a model of a quasi bipolar liquid crystal droplet, where nematic order from the anisotropic actin filaments competes with isotropic interfacial energy from the FUS, controlling droplet shape in a size-dependent manner. Our results demonstrate a versatile approach to construct tunable, anisotropic macromolecular liquids. 

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4. Targeting diffuse midline gliomas: The promise of focused ultrasound-mediated blood-brain barrier opening

   https://doi.org/10.1016/j.jconrel.2023.11.037  

   Martinez, Payton J; Green, Adam L; Borden, Mark A (January 2024, Journal of Controlled Release)

   Diffuse midline gliomas (DMGs), including diffuse intrinsic pontine glioma, have among the highest mortality rates of all childhood cancers, despite recent advancements in cancer therapeutics. This is partly because, unlike some CNS tumors, the blood-brain barrier (BBB) of DMG tumor vessels remains intact. The BBB prevents the permeation of many molecular therapies into the brain parenchyma, where the cancer cells reside. Focused ultrasound (FUS) with microbubbles has recently emerged as an innovative and exciting technology that non-invasively permeabilizes the BBB in a small focal region with millimeter precision. In this review, current treatment methods and biological barriers to treating DMGs are discussed. State-of-the-art FUS-mediated BBB opening is then examined, with a focus on the effects of various ultrasound parameters and the treatment of DMGs. 

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5. Electrospinning of Heterogeneous Nanofibers: A Review

   https://doi.org/10.1149/2754-2734/ad86cc  

   Regmi, Dinkar; Choi, Jin_Woo; Xu, Jian (October 2024, ECS Advances)

   Electrospinning is a straightforward approach for efficiently creating continuous fibers within the submicron to nanometer size range. Electrospun fibers possess excellent properties like high porosity, large specific surface area, tunable morphology, small diameter, etc., making them desirable in various applications. Because of its various properties, polymer is one of the most used materials as the spinning solution in electrospinning. Electrospun polymeric fibers, by themselves, may serve limited applications. Therefore, they are usually mixed with other materials to serve many applications. There are many ways in which these other materials are mixed with polymers in electrospinning, like doping, surface treatment, functionalization, etc. There are several studies published that report on the various composite fibers produced using electrospinning. However, a review focused solely on the production of heterogeneous fibers, where the electrospun fibers are intrinsically made of more than one material, is lacking. Herein, we review different heterogeneous fibers synthesized using electrospinning and their fabrication methods. 

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