Abstract: Provided herein are systems comprising Class2, Type V CRISPR polypeptides, guide nucleic acids (gNA), and optionally donor template nucleic acids useful in the modification of a PCSK9 gene. The systems are also useful for introduction into cells, for example eukaryotic cells having mutations in the PCSK9 gene. Also provided are methods of using such CasX:gNA systems to modify cells having such mutations.

Abstract: Provided herein are reference guide nucleic acid scaffolds and variants of reference guide nucleic acid scaffolds capable of binding one or more engineered proteins comprising a RuvC cleavage domain. In some embodiments, the variants of the reference guide nucleic acid scaffolds comprise at least one modification compared to the reference guide nucleic acid scaffold sequences and exhibit one or more improved characteristics compared to the reference guide nucleic acid scaffolds.

Abstract: Provided herein are CasX:gNA systems comprising CasX polypeptides, guide nucleic acids (gNA), and optionally donor template nucleic acids useful in the modification of a SOD1 gene. The systems are also useful for introduction into cells, for example eukaryotic cells having mutations in the SOD1 protein or the SOD1 regulatory element. Also provided are methods of using such CasX:gNA systems to modify cells having such mutations and utility in methods of treatment of a subject with a SOD1-related disease.

Abstract: Provided herein are CasX:gNA systems, and compositions and methods relating thereto, the systems comprising CasX proteins, guide nucleic acids (gNAs), and optionally donor template nucleic acids useful for the modification cell genes encoding proteins involved in antigen processing, antigen presentation, antigen recognition, and/or antigen response, as well as methods of producing and using populations of cells comprising these modified genes. In some embodiments, the modified cells further express chimeric antigen receptors (CAR) or engineered T cell receptors (TCR). Such systems are useful for preparing cells for immunotherapy.

Abstract: Provided herein are engineered Class 2, Type V nucleases and guide RNAs useful for the editing of target nucleic acids. Also provided are methods of making and using such variants to modify nucleic acids.

Abstract: Provided herein are CRISPR:guide systems comprising Class 2 Type V polypeptides (e.g. CasX:gNA systems comprising CasX polypeptides), guide nucleic acids (gNA), and optionally donor template nucleic acids useful in the modification of a HTT gene. The systems are also useful for introduction into cells, for example eukaryotic cells having mutations in the huntingtin protein. Also provided are methods of using such systems to modify cells having such mutations and utility in methods of treatment of a subject with a HTT-related disease, such as Huntington's disease.

Abstract: Provided herein are Class 2 Type V CRISPR:gNA systems comprising Class 2 Type V CRISPR polypeptides (e.g. CasX), guide nucleic acids (gNA), and optionally donor template nucleic acids useful in the modification of a RHO gene. The systems are also useful for introduction into cells, for example eukaryotic cells having mutations in the rhodopsin protein. Also provided are methods of using such systems to modify cells having such mutations and utility in methods of treatment of a subject with a RHO-related disease, such as retinitis pigmentosa.

Abstract: Provided herein are engineered proteins comprising a RuvC DNA cleavage domain comprising one or more amino acid modifications, and one or more improved characteristics, relative to a naturally occurring RuvC domain. Also provided are gene editing systems comprising engineered proteins, and methods for use thereof.

Abstract: Provided herein are Class 2 Type V CRISPR:gNA systems comprising Class 2 Type V CRISPR polypeptides (e.g. CasX), guide nucleic acids (gNA), and optionally donor template nucleic acids useful in the modification of a RHO gene. The systems are also useful for introduction into cells, for example eukaryotic cells having mutations in the rhodopsin protein. Also provided are methods of using such systems to modify cells having such mutations and utility in methods of treatment of a subject with a RHO-related disease, such as retinitis pigmentosa.

Abstract: Provided herein are CasX:gNA systems comprising CasX polypeptides, guide nucleic acids (gNA), and optionally donor template nucleic acids useful in the modification of a SOD1 gene. The systems are also useful for introduction into cells, for example eukaryotic cells having mutations in the SOD1 protein or the SOD1 regulatory element. Also provided are methods of using such CasX:gNA systems to modify cells having such mutations and utility in methods of treatment of a subject with a SOD1-related disease.

Abstract: A retractor system includes one or more blades, a handle, and a frame. The handle includes first and second arms with jaw portions and recesses configured to removably retain a blade. Both arms include rotatable connections and handles, where the rotatable connections are between jaw portions and handles. The rotatable connections are connected together such that the arms are rotatable with respect to one another. In one embodiment, the recesses are partial disc shapes opposed to one another, such that when the jaw portions are in a closed position, a disc-shaped space is present between the jaw portions in the closed position. The blade includes a corresponding disc-shape protrusion that may be retained in the recesses, and in some embodiments may include one or more notches to mate with a protrusion in a recess that prevents blade rotation while in the handle.

Abstract: Provided herein are engineered CasX systems and components thereof, including variant CasX proteins and variant guide nucleic acids (gNAs). The variant CasX proteins and variant gNAs of the disclosure display at least one improved characteristic when compared to a reference CasX protein or reference gNA of the disclosure. In some instances, the variants have one or more improved CasX ribonucleoprotein complex functions. Also provided are methods of making and using said variants.

Abstract: Provided herein are methods of developing biomolecule variants (such as proteins, RNA, or DNA) with improved characteristics, for example by developing libraries of variants with alterations to one or more specific monomer locations and screening said libraries for characteristics of interest. These alterations can include deletion, substitution, and insertion, and variants may comprise one alteration or a combination of alterations. Said methods may include further iterative cycles of library construction and evaluation to develop, for example, a biomolecule variant with improved characteristics compared to a reference biomolecule. The methods can also provide information that may be used in the rational design of variants.

Abstract: A retractor system includes one or more blades, a handle, and a frame. The handle includes first and second arms with jaw portions and recesses configured to removably retain a blade. Both arms include rotatable connections and handles, where the rotatable connections are between jaw portions and handles. The rotatable connections are connected together such that the arms are rotatable with respect to one another. In one embodiment, the recesses are partial disc shapes opposed to one another, such that when the jaw portions are in a closed position, a disc-shaped space is present between the jaw portions in the closed position. The blade includes a corresponding disc-shape protrusion that may be retained in the recesses, and in some embodiments may include one or more notches to mate with a protrusion in a recess that prevents blade rotation while in the handle.

Abstract: Provided herein are CasX:gNA systems comprising CasX polypeptides, guide nucleic acids (gNA), and optionally donor template nucleic acids useful in the modification of a SOD1 gene. The systems are also useful for introduction into cells, for example eukaryotic cells having mutations in the SOD1 protein or the SOD1 regulatory element. Also provided are methods of using such CasX:gNA systems to modify cells having such mutations and utility in methods of treatment of a subject with a SOD1-related disease.

Abstract: Provided herein are engineered proteins. In some embodiments, the engineered proteins comprise a RuvC DNA cleavage domain comprising one or more modifications, relative to a naturally occurring domain. In some embodiments, the engineered proteins comprise a chimeric domain, for example a chimeric helical I domain. In some embodiments, the engineered proteins are chimeric proteins, comprising at least two domains, each domain derived from a different source, for example derived from SEQ ID NO: 1 and SEQ ID NO: 2. Also provided are systems comprising these engineered proteins, and methods of making and using said engineered proteins.

Abstract: The present disclosure provides an RNA-guided effector polypeptide having a length that is less than Streptococcus pyogenes Cas9, and that retains the ability, when complexed with a guide RNA, to bind to a target nucleic acid. The present disclosure provides a fusion polypeptide comprising: i) an RNA-guided effector polypeptide of the present disclosure; and ii) a fusion partner. The present disclosure further provides nucleic acids encoding an RNA-guided effector polypeptide, or a fusion polypeptide, of the present disclosure. Methods of using an RNA-guided effector polypeptide, or a fusion polypeptide, of the present disclosure are also provided.

Abstract: A system and method for analyzing bio-fluid constituents and properties in a bio-fluid sample, wherein the system comprises a bio-fluid collection apparatus, a bio-fluid testing/analysis apparatus, and a reporting apparatus.

Abstract: According to example embodiments, there is provided a handheld mobile computing device, for example a smartphone, includes a computing system, a motion detector, a global positioning system receiver, and a touch-screen display to display a user interface and detect user selections from the user interface. A usage goal-setting user interface includes a dashboard and a plurality of user-selectable menu options, the usage goal-setting user interface including display elements allowing a user to enter one or more parameters respecting the goals including physical activity usage goals, social activity usage goals, educational usage goals, and mindfulness usage goals.

Abstract: A greeting card having a mobile object releasably attached thereto. The mobile object may be shaped like a character or object with one or more wheels at a bottom surface thereof. The mobile object may be removed from the greeting card and set upright onto a surface. Activating a motor module within the mobile object causes the one or more wheels to rotate, setting the mobile object rolling along said surface.