This invention relates generally to Bottlebrush polymeric delivery systems. The present polymeric delivery systems may be complexed with biological agents, including nucleic acids, peptides, proteins, or small molecules, for delivery to cells. In particular, the present polymeric delivery systems may be used for delivery of Cas protein in gene editing.

The present disclosure relates to deoxyribonucleic acid (DNA) editing agents, and their use in preparing genetically modified cells and birds. The present disclosure further relates to fertile genetically modified avians and genetically modified avian primordial germ cells (PGCs) for producing sterile genetically modified avians (birds) that can serve as surrogate hosts for donor PGCs. The present disclosure further relates to methods for producing fertile avian strains that can produce a population of embryos and offspring, in both sexes, all of which are sterile and viable, and further relates to their subsequent use as sterile surrogate hosts for donor PGCs.

Modifications of maize genes Zm1d31079 and Zm1d44812 which provide maize plants with reduced height are disclosed. Maize plants comprising a modified Zm1d31079 or Zm1d44812 with a heterologous enhancing element are described. Also disclosed are seed obtained from such plants as well as use of the seed and plants to produce commodity productions and in maize breeding.

Provided herein are fusion proteins and associated methods and systems for increasing the efficiency of genome editing using site-directed nucleases. The fusion proteins, systems, and methods can selectively increase desired editing outcomes (e.g., inversion, excision, and homology-directed repair). Also provided are various useful compositions for the production and use of the fusion proteins and practice of the methods.

The present invention relates to a novel CRISPR system comprising i) at least one nucleotide sequence encoding at least one Cas13 protein; and ii) at least one gRNA or at least one nucleotide sequence encoding said at least one gRNA capable of hybridizing with one or more viral target RNA molecules, wherein said system comprises a viral 5 UTR or a nucleotide sequence encoding said 5 UTR and/or a viral 3 UTR or a nucleotide sequence encoding said viral 3 UTR, wherein a viral replicase recognition sequence is comprised in at least any one of said 5 UTR or in the nucleotide sequence encoding said 5 UTR, or said 3 UTR or in the nucleotide sequence encoding said 3 UTR, and wherein said system does not comprise a nucleotide sequence encoding a viral replicase and wherein said viral replicase recognition sequence is from the same RNA virus as the one or more viral target RNA molecules. The present invention also relates to a delivery system comprising the novel system and a composition comprising the novel system or the delivery system. The present invention further relates to the medical use of the novel system or in particular to the system for use in a method of preventing or treating a viral disease in a subject. Additionally, the present invention also relates to a kit comprising the novel system and to a method of producing the novel system.

Provided herein are regulatory elements capable of restricting the expression of a heterologous nucleotide sequence to specific neuronal populations and regions of the central nervous system (CNS). Further provided herein are vectors comprising such regulatory elements and uses of such regulatory elements and vectors for selective expression in the CNS.

The present disclosure provides proteolysis targeting chimeras-based scalable CID (PROTAC-CID) system that repurpose PROTACs for inducible, orthogonal, and multiplex transcriptional activation. When coupled with multi-layer genetic circuits, PROTAC-CID enables digitally inducible DNA manipulations with low basal levels. These PROTAC-CID systems can be delivered in vivo by adeno-associated virus (AAV) to allow ON-OFF genetic switches.

Nucleic acid constructs and compositions that allow insertion of an argininosuccinate synthase 1 (ASS1) coding sequence into a target genomic locus such as an endogenous ASS1 locus and/or expression of the ASS1 coding sequence are provided. Also provided are nuclease agents (e.g., targeting an endogenous ASS1 locus) or nucleic acids encoding nuclease agents to facilitate integration of the nucleic acid constructs into a target genomic locus such as an endogenous ASS1 locus. The nucleic acid constructs and compositions can be used in methods of introducing an ASS1 nucleic acid into a cell, methods of integration of an ASS1 nucleic acid into a target genomic locus, methods of expression of ASS1 in a cell, and in methods of treating citrullinemia type I or ASS1 deficiency in a subject.

The present disclosure provides endonuclease variants having improved properties, such as hyperactivity and/or low indiscriminate single strand DNase activity, relative to the corresponding wild-type endonucleases.

Provided herein are compositions, systems, and kits comprising effector domains for activating and silencing gene expression. In particular, synthetic transcription factors comprising the effector domains are provided.