Abstract: Methods and compositions for inducing a plurality of mutations in transgenic Cas9 eukaryotes to model a neuronal disease or disorder. The invention further comprehends testing putative treatments with such models, e.g., testing putative chemical compounds that may be pharmaceutically relevant for treatment or gene therapy that may be relevant for treatment, or combinations thereof. The invention allows for the study of genetic diseases and putative treatments to better understand and alleviate a genetic disease or a condition, e.g., autism, autism-spectrum disease or disorder, obsessive-compulsive disorder, or psychiatric disorders.

Abstract: The present invention features compositions and methods for editing deleterious mutations associated with hemoglobinopathies, such as sickle cell disease (SCD). In particular embodiments, the invention provides methods for correcting mutations in a beta globin polynucleotide using modified adenosine base editors termed “ABE8” having unprecedented levels (e.g., >60-70%) of efficiency.

Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA. Methods for making and using and uses of such systems, methods, and compositions and products from such methods and uses are also disclosed and claimed.

Abstract: The disclosure provides compositions comprising novel adenosine base editors (e.g., ABE8) that have increased efficiency and methods of using these adenosine deaminase variants for editing a target sequence.

Abstract: The present invention features compositions and methods for editing deleterious mutations associated with hemoglobinopathies, such as sickle cell disease (SCD). In particular embodiments, the invention provides methods for correcting mutations in a beta globin polynucleotide using modified adenosine base editors termed “ABE8” having unprecedented levels (e.g., >60-70%) of efficiency.

Abstract: The invention features nucleobase editors and multi-effector nucleobase editors having an improved editing profile with minimal off-target deamination, compositions comprising such editors, and methods of using the same to generate modifications in target nucleobase sequences.

Abstract: The invention provides compositions comprising novel adenosine base editors (e.g., ABE8) that have increased efficiency and methods of using base editors comprising adenosine deaminase variants for altering mutations associated with Glycogen Storage Disease Type 1a (GSD1a).

Abstract: The invention features compositions and methods for treating, reducing, or ameliorating the debilitating effects of Amyotrophic Lateral Sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA). Provided herein are compositions and methods of using improved new base editors (e.g., adenosine base editors) comprising a polynucleotide programmable nucleotide binding domain and a nucleobase editing domain in conjunction with a guide polynucleotide to disrupt normal transcription of a gene associated with a genetic disease or condition, e.g. ALS, or SBMA by modifying a target gene associated with the genetic disorder or condition with a base editor system provided herein.

Abstract: The invention features base editors having reduced non-target deamination, methods of using the base editors, and assays for characterizing base editors as having decreased non-target deamination, e.g. compared to programmed, on-target deamination.

Abstract: The disclosure provides compositions comprising novel adenosine base editors (e.g., ABE8) that have increased efficiency and methods of using these adenosine deaminase variants for editing a target sequence.

Abstract: Disclosed are compositions and methods involving nucleic acid assemblies that enclose and/or protect cargo. Disclosed are compositions that include a nucleic acid assembly comprising one or more nucleic acid molecules and cargo comprising two or more cargo molecules. The nucleic acid assembly can have physiochemical properties that: (i) enhance targeting of the composition to one or more types of cells, tissues, organs, or microenvironments relative to other types of cells, tissues, organs, or microenvironments in vivo; (ii) enhance stability and/or half-life of the composition in vivo; and/or (iii) reduce immunogenicity of the composition. The nucleic acid assembly and/or cargo can have features that enhance intracellular trafficking of nucleic acid assembly and/or its cargo. The cargo can be enclosed and/or protected by the nucleic acid assembly. Some or all of the cargo molecules in the composition can be present in a defined stoichiometric ratio.

Abstract: The present invention features compositions and methods for editing deleterious mutations associated with hemoglobinopathies, such as sickle cell disease (SCD). In particular embodiments, the invention provides methods for correcting mutations in a beta globin polynucleotide using modified adenosine base editors termed “ABE8” having unprecedented levels (e.g., >60-70%) of efficiency.

Abstract: The present invention features compositions and methods for editing deleterious mutations associated with hemoglobinopathies, such as sickle cell disease (SCD). In particular embodiments, the invention provides methods for correcting mutations in a beta globin polynucleotide using modified adenosine base editors termed “ABE8” having unprecedented levels (e.g., >60-70%) of efficiency.

Abstract: The present invention features compositions and methods for editing deleterious mutations associated with hemoglobinopathies, such as sickle cell disease (SCD). In particular embodiments, the invention provides methods for correcting mutations in a beta globin polynucleotide using modified adenosine base editors termed “ABE8” having unprecedented levels (e.g., >60-70%) of efficiency.

Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA. Methods for making and using and uses of such systems, methods, and compositions and products from such methods and uses are also disclosed and claimed.

Abstract: The disclosure provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered RNA-targeting systems comprising a novel RNA-targeting Cas12b effector protein and at least one targeting nucleic acid component like a guide RNA or crRNA.

Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA. Aspects of the invention in particular relate to Cpf1 mutants having altered PAM specificity.

Abstract: The disclosure provides compositions comprising novel adenosine base editors (e.g., ABE8) that have increased efficiency and methods of using these adenosine deaminase variants for editing a target sequence.

Abstract: The present disclosure provides for systems, methods, and compositions for targeting and editing nucleic acids. In particular, the present disclosure provides non-naturally occurring or engineered RNA-targeting systems comprising a RNA-targeting Cas13 protein, at least one guide molecule, and at least one adenosine deaminase protein or catalytic domain thereof.

Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA. Methods for making and using and uses of such systems, methods, and compositions and products from such methods and uses are also disclosed and claimed.