Abstract: Disclosed herein are novel variants of clotting factors VII, VIII, and IX and their use, for example, in methods of treating a subject with a clotting disorder, such as hemophilia A or hemophilia B.

Abstract: Provided herein are compositions and methods for promoting hematopoietic cell cytotoxicity.

Abstract: Provided herein are nucleic acids, vectors, and cells containing an expression-optimized codon that encodes a Munc13-4 polypeptide or a STXBP2 polypeptide. Also provided are methods of making and using the nucleic acids, vectors, and cells. Also provided herein are methods of treating of Hemophagocytic Lymphohistiocytosis (HLH) in a subject.

Abstract: Provided herein are recombinant AAV (rAAV) serotypes that are useful for targeting innate immune cells. In some embodiments, the rAAV are used to deliver genes encoding one or more receptors that can target the innate immune cells to diseased tissue of interest. In some aspects, the rAAV particle is a rAAV particle having a mutation in a surface-exposed amino acid, such as tyrosine, threonine, or serine, that enhances transduction of dendritic cells.

Abstract: Disclosed herein are novel variants of clotting factors VII, VIII, and IX and their use, for example, in methods of treating a subject with a clotting disorder, such as hemophilia A or hemophilia B.

Abstract: A recombinant von Willebrand Factor (VWF) protein comprising one or more mutations and uses thereof are described. A recombinant protein complex comprising a von Willebrand factor sequence and one artificial Factor VIII sequence is described. A recombinant protein complex comprising a Factor VIII sequence and one artificial von Willebrand sequence is described. A recombinant protein complex is described that includes one artificial von Willebrand factor sequence and one artificial Factor VIII sequence. Also described are nucleic acid sequences and a vector encoding a VWF sequence and a pharmaceutical composition for inducing blood clotting that includes a VWF protein.

Abstract: This disclosure relates to engineered cells, such as T-cells, comprising targeted chimeric antigen receptors. In certain embodiments, T-cell targeted chimeric antigen receptors (CAR) are expressed at higher levels when endogenous expression of a T-cell antigen is knocked-down or reduced in the T-cells. In certain embodiments, the engineered cells are immunoregulatory cells genetically modified to prevent or reduce T-cell antigen expression, or the immunoregulatory cells contain a nucleic acid that reduces or knocksdown T-cell mRNA expression, under conditions such that reduced expression of the T-cell antigen results in an increased expression of a chimeric antigen receptor compared to similarly situated immunoregulatory cells wherein the expression of the T-cell antigen is not altered or reduced. In certain embodiments, T-cell antigens include, but are not limited to, CD5, CD7 and CD3.

Abstract: This disclosure relates to recombinant or chimeric FVIII proteins, variants, and vectors encoding the proteins containing one or more ancestral mutations. In certain embodiments, one or more protein domains comprise amino acid sequences that are derived from ancestrally reconstructed amino acid sequences. In certain embodiments, the disclosure relates to pharmaceutical compositions comprising the proteins or vectors and related methods of inducing blood clotting.

Abstract: The systems and methods are directed to leveraging the channel geometry and configuration to overcome diffusion limitations of current transduction systems. The methods may include a method of transducing target cells using a device. The device may include at least one continuous channel. The method may include delivering target cells and viral vectors into a transduction region of the channel. After transducing for some incubation time, a flushing solution may be delivered. The method may include collecting transduced cells after the transducing incubation time and the delivering of the flushing solution.

Abstract: This disclosure relates to recombinant or chimeric FVIII proteins, variants, and vectors encoding the proteins containing one or more ancestral mutations. In certain embodiments, one or more protein domains comprise amino acid sequences that are derived from ancestrally reconstructed amino acid sequences. In certain embodiments, the disclosure relates to pharmaceutical compositions comprising the proteins or vectors and related methods of inducing blood clotting.

Abstract: The systems and methods are directed to leveraging the channel geometry and configuration to overcome diffusion limitations of current transduction systems. The methods may include a method of transducing target cells using a device. The device may include at least one continuous channel. The method may include delivering target cells and viral vectors into a transduction region of the channel through a first inlet/outlet simultaneously and/or consecutively when one or more additional inlets/outlets that are located in a region of the channel downstream of the transduction are closed. After transducing for some incubation time, a flushing solution may be delivered through one or more of the additional inlets/outlets. The method may include collecting transduced cells after the transducing incubation time and the delivering of the flushing solution.

Abstract: Embodiments of the present invention provide an integrated digital control apparatus (10) for a stringed musical instrument. In some embodiments, the apparatus (10) generally includes an input (26) coupled with at least a portion of the musical instrument, a digital control element (28) coupled with at least one of the instrument's pickups, and a controller (30) coupled with the input (26) and the digital control element (28). The controller (30) is operable to control the digital control element (28) to vary at least one characteristic of the signal generated by the pickup in response to functioning of the input (26) by a musician. Such a configuration enables the musician to easily vary signal characteristics, such as volume or tone, while playing the instrument.

Abstract: Embodiments of the present invention provide an integrated digital control apparatus (10) for a stringed musical instrument. In some embodiments, the apparatus (10) generally includes an input (26) coupled with at least a portion of the musical instrument, a digital control element (28) coupled with at least one of the instrument's pickups, and a controller (30) coupled with the input (26) and the digital control element (28). The controller (30) is operable to control the digital control element (28) to vary at least one characteristic of the signal generated by the pickup in response to functioning of the input (26) by a musician. Such a configuration enables the musician to easily vary signal characteristics, such as volume or tone, while playing the instrument.