The invention relates to compositions and methods that can target B cells and/or hematopoietic stem cells (HSCs) in order to engineer those cells to express specific antibodies ex vivo or in vivo and become part of the host's long-lived immune repertoire.

The present disclosure provides methods for enhancing the rate of homology-directed repair (HDR) during genomic editing in primary cells.

The present invention provides a method for detecting a target nucleic acid by cleaving a non-natural sequence using a Cas13 protein, belonging to the technical field of biology. The Cas13 protein belongs to the Cas13b protein family; and the non-natural sequence includes a chimeric sequence composed of a ribonucleotide and a deoxyribonucleotide. The present invention provides a system for detecting a target nucleic acid. The system includes a chimeric sequence and a Cas13 protein guided by crRNA. Moreover, it is verified that the detection effect of the Cas13-chimeric sequence system is comparable to that of a conventional Cas13-ssRNA system, and the former is even superior to the latter under certain circumstances. The present invention combines amplification technology with the system, enabling the detection limit of the system to reach an aM level. In summary, the present invention provides a new option for the field of nucleic acid detection, and meanwhile also broadens the use of the Cas13 protein and the non-natural sequence.

Provided are methods and systems for detection of oral bacteria.

The invention relates to a chimeric protein comprising three covalently linked domains including a RNA-guided DNA endonuclease, a flexible peptide linker, and a switchable receptor binding domain. The endonuclease activity depends on the uncaging of a caged specific ligand of said switchable receptor binding domain. Methods for inducing nuclear translocation of the chimeric protein and inducing the modification of an endogenous gene in a eukaryotic cell are also disclosed.

Provided is a programmable adenine base editor and system comprising the same and method of using the same. Also provided are MPG and mutants thereof, which can be used in the programmable adenine base editor.

Provided herein are chimeric minigenes, where the alternative splicing of the minigene determines whether an encoded gene is expressed. In particular, the minigenes are alternatively spliced in response to splicing modulator drugs, such that the encoded gene is only expressed in the present of the splicing modulator drug. The encoded gene may encode an inhibitory RNA, a CRISPR-Cas9 protein, a transactivator, or a therapeutic protein.

The invention relates to modulating the function of a regulatory element in a nucleic acid, comprising delivering to a cell a catalytically inactive Cas13 (dCas13) protein and a CRISPR RNA (crRNA), wherein the crRNA recruits the dCas13 protein to the regulatory element, such that the dCas13 protein sterically blocks the regulatory element.

Compositions and methods for modifying genomic DNA sequences are provided. The methods produce double-stranded breaks (DSBs) at pre-determined target sites in a targeted DNA sequence, resulting in mutation, insertion, and/or deletion of DNA sequences at the targeted site(s). Compositions comprise DNA constructs comprising nucleotide sequences that encode a Cpf1 protein operably linked to a promoter that is operable in the cells of interest. The DNA constructs can be used to direct the modification of genomic DNA at pre-determined locations. Methods to use these DNA constructs to modify genomic DNA sequences are described herein. Additionally, compositions and methods for modulating the expression of genes are provided. Compositions comprise DNA constructs comprising a promoter that is operable in the cells of interest operably linked to nucleotide sequences that encode a mutated Cpf1 protein with an abolished ability to produce DSBs, optionally linked to a domain that regulates transcriptional activity. The methods can be used to up- or down-regulate the expression of genes at predetermined genomic loci.

Disclosures herein are directed to compositions comprising single guide RNA (sgRNA) and fusion proteins comprising a Cas9 nickase and deaminase designed for a CRISPR-Cas9 system and method of using thereof for preventing, ameliorating or treating one or more cardiomyopathies.