Abstract: Temperature sensitive transcriptional bioswitches and related genetic circuits and in particular bandpass and/or multiplex genetic circuits, vectors, cells, compositions methods and systems are described.

Abstract: Aspects disclosed herein include an implantable, detachable, and removable medical device comprising: a therapeutic balloon configured to perform a therapeutic activity inside a living subject; and a focused-ultrasound activatable actuator operably connected to the therapeutic balloon; wherein the actuator is capable of being activated between a closed state and an open state remotely via a focused ultrasound beam; wherein the device is configured to be in an implantation state to facilitate implantation of the device in the living subject, in a therapeutic state to facilitate performance of the therapeutic activity, and subsequently in an expulsion state to facilitate expulsion of the medical device from the living subject; and wherein the implantation state, therapeutic state, and expulsion state are different from each other

Abstract: Aspects disclosed herein include a composite material comprising: one or more shape memory polymers; and a first additive provided in the shape memory polymer(s); wherein: the first additive increases one or more ultrasound-absorption characteristics of the composite material compared to that of the same shape memory polymer(s) free of said first additive; the composite material is characterized by a composite transition temperature (Tcm,trans); and the composite material or one or more portions thereof undergo a shape change from a temporary shape to a permanent shape when the composite material or said one or more portions thereof are heated to within 35° C. of Tcm,trans or a temperature approximately equal to or greater than Tcm,trans.

Abstract: Disclosed herein include methods, compositions, and kits suitable for use in dynamic non-destructive imaging. The non-destructive imaging can be nonlinear ultrasound imaging. There are provided, in some embodiments, nucleic acid compositions encoding gas vesicles (GVs) capable of producing nonlinear ultrasound contrast upon expression in a prokaryotic cell (e.g., a probiotic bacterial cell) or a eukaryotic cell (e.g., a therapeutic mammalian cell).

Abstract: Disclosed herein include methods, compositions, and kits suitable for use in sorting a population of cells. In some embodiments, the method comprises flowing a fluid sample comprising a population of cells through a microfluidic channel. The population of cells can be configured to express gas vesicles (GVs) in a context-dependent manner. The expression of GVs within a cell can increase the compressibility (?) and reduce the density (?) of said cell, thereby modulating the acoustic contrast (?) of said cell relative to the fluid in the microfluidic channel. The method can comprise applying ultrasound to the microfluidic channel. Applying ultrasound can generate acoustic standing wave(s) in the microfluidic channel, thereby positioning pressure antinode(s) in the microfluidic channel.

Abstract: A method of analyzing a tumor sample comprising: (a) acquiring a library comprising a plurality of tumor members from a tumor sample; (b) contacting the library with a bait set to provide selected members; (c) acquiring a read for a subgenomic interval from a tumor member from said library; (d) aligning said read; and (e) assigning a nucleotide value (e.g., calling a mutation) from said read for the preselected nucleotide position, thereby analyzing said tumor sample.

Abstract: Disclosed herein include methods, compositions, and kits suitable for use in calcium imaging. There are provided, in some embodiments, Ca2+-sensing GvpC proteins. Disclosed herein include Ca2+-sensing gas vesicles (GVs) comprising Ca2+-sensing GvpC proteins. In some embodiments, the Ca2+-sensing GvpC protein is capable of undergoing a first allosteric conformational change upon the Ca2+-binding domain binding Ca2+ that causes the Ca2+-sensing GV to change from a GV stiff state to a GV soft state. One or more of the mechanical, acoustic, surface, and magnetic properties of a Ca2+-sensing GV can differ between the GV soft state and the GV stiff state.

Abstract: Disclosed herein include methods, compositions, and kits suitable for use in spatiotemporal regulation of therapeutic macrophages through a combination of molecular and physical actuation. There are provided, in some embodiments, thermal bioswitches that allow macrophages to sense small changes in temperature and use them as inputs for the actuation of genetic circuits. Genetic circuits capable of inducing expression of a payload upon thermal stimulation are provided. There are provided, in some embodiments, heat-inducible macrophages and methods of using are provided.

Abstract: Disclosed herein include methods, compositions, and kits suitable for use in imaging of in situ gene expression. There are provided, in some embodiments, viral vector compositions. Disclosed herein includes a single viral vector comprising one or more gas vesicle assembly (GVA) gene(s) encoding one or more GVA protein(s), and one or more gas vesicle structural (GVS) gene(s) encoding one or more GVS protein(s). The one or more GVA protein(s) and the one or more GVS protein(s) can be capable of forming gas vesicles (GVs) upon expression in a cell.

Abstract: Disclosed herein include adeno-associated virus (AAV) acoustic targeting peptides. An AAV comprising the AAV acoustic targeting peptide can exhibit increased transduction at site(s) of focused ultrasound blood-brain barrier opening (FUS-BBBO), increased neuronal tropism, and diminished transduction of peripheral organs. Disclosed herein include recombinant adeno-associated virus (rAAV) comprising an AAV acoustic targeting peptide disclosed herein. Also provided herein include methods of delivering an agent to one or more target brain region(s) of a subject.

Abstract: Disclosed herein include methods, compositions, and kits enabling expression of multiple proteins from a single mRNA with a predetermined stoichiometry. There are provided, in some embodiments, nucleic acid compositions comprising a promoter operably linked to a polynucleotide comprising a first nucleic acid unit encoding first unit payload protein(s) and a second nucleic acid unit encoding second unit payload protein(s). The first nucleic acid unit and the second nucleic acid unit can each comprise a 3? engineered translation initiation site (eTIS) comprising a three-nucleotide tunable element immediately upstream of a start codon. The eTIS of each of the first nucleic acid unit and the second nucleic acid unit can be configured to achieve a predetermined stoichiometry of the first unit payload protein(s) and the second unit payload protein(s) in a cell or cell-like environment.

Abstract: Disclosed herein include methods, compositions, and kits suitable for use in spatiotemporal regulation of probiotic cells. There are provided, in some embodiments, thermal bioswitches that allow probiotic cells to sense small changes in temperature and use them as inputs for the actuation of genetic circuits. Genetic circuits capable of inducing expression of a payload upon thermal stimulation are provided. Thermally actuated probiotic cells and methods of use for the treatment of diseases or disorders are also provided.

Abstract: A method of analyzing a tumor sample comprising: (a) acquiring a library comprising a plurality of tumor members from a tumor sample; (b) contacting the library with a bait set to provide selected members; (c) acquiring a read for a subgenomic interval from a tumor member from said library; (d) aligning said read; and (e) assigning a nucleotide value (e.g., calling a mutation) from said read for the preselected nucleotide position, thereby analyzing said tumor sample.

Abstract: Provided herein are methods, systems, and related vectors and compositions allowing for noninvasive control of neural circuits. In particular, the methods and systems herein described utilize acoustically targeted chemogenetics to achieve a noninvasive neuromodulation in specifically selected cell-types among spatially selected brain regions.

Abstract: Systems and methods for targeting specific cell types by selective application of ultrasonic harmonic excitation at a resonance frequency (“oncotripsy”) for the specific cell types are presented. The systems and the methods result in permeabilization, lysis, and/or death of the targeted specific cell types by using ultrasonic harmonic excitations that have a frequency and a pulse duration specifically tuned to disrupt nuclear membranes of the targeted specific cell types by inducing a destructive vibrational response therein while leaving non-targeted cell types intact. Target cells may be neoplastic.

Abstract: A method of analyzing a tumor sample comprising: (a) acquiring a library comprising a plurality of tumor members from a tumor sample; (b) contacting the library with a bait set to provide selected members; (c) acquiring a read for a subgenomic interval from a tumor member from said library; (d) aligning said read; and (e) assigning a nucleotide value (e.g., calling a mutation) from said read for the preselected nucleotide position, thereby analyzing said tumor sample.

Abstract: Hybrid gas vesicle gene cluster (GVGC) configured for expression in a prokaryotic host are described comprising gas vesicle assembly (GVA) genes native to a GVA prokaryotic species and capable of being expressed in a functional form in the prokaryotic host, and one or more gas vesicle structural (GVS) genes native to one or more GVS prokaryotic species, at least one of the one or more GVS prokaryotic species different from the GVA prokaryotic species, and related gas vesicle reporting (GVR) genetic circuits, genetic, vectors, engineered cells, and related compositions methods and systems to produce GVs, hybrid GVGC and/or image a target site.

Abstract: A method of analyzing a tumor sample comprising: (a) acquiring a library comprising a plurality of tumor members from a tumor sample; (b) contacting the library with a bait set to provide selected members; (c) acquiring a read for a subgenomic interval from a tumor member from said library; (d) aligning said read; and (e) assigning a nucleotide value (e.g., calling a mutation) from said read for the preselected nucleotide position, thereby analyzing said tumor sample.

Abstract: Hybrid gas vesicle gene cluster (GVGC) configured for expression in a prokaryotic host are described comprising gas vesicle assembly (GVA) genes native to a GVA prokaryotic species and capable of being expressed in a functional form in the prokaryotic host, and one or more gas vesicle structural (GVS) genes native to one or more GVS prokaryotic species, at least one of the one or more GVS prokaryotic species different from the GVA prokaryotic species, and related gas vesicle reporting (GVR) genetic circuits, genetic, vectors, engineered cells, and related compositions methods and systems to produce GVs, hybrid GVGC and/or image a target site.

Abstract: Temperature sensitive transcriptional bioswitches and related genetic circuits and in particular bandpass and/or multiplex genetic circuits, vectors, cells, compositions methods and systems are described.