Described herein are systems and methods for modulating gene expression. Also described herein are systems and methods for treating a disease or a condition by modulating gene expression.

Disclosed herein are lipid nanoparticles comprising plurality of lipids, a targeting moiety for an HIV-1 chemokine receptor, and a CRISPR nucleic acid complementary to an HIV-1 gene, pharmaceutical compositions and methods of use thereof.

The present invention relates to the field of nucleic acid editing, in particular to the field of clustered regularly interspaced short palindromic repeat (CRISPR) technology. Specifically, the present invention relates to Cas effector proteins, fusion proteins comprising such proteins, and nucleic acid molecules encoding them. The present invention also relates to complexes and compositions for nucleic acid editing (e.g., gene or genome editing), which comprise the proteins or fusion proteins of the present invention, or nucleic acid molecules encoding them. The present invention also relates to a method for nucleic acid editing (e.g., gene or genome editing), which uses the proteins or fusion proteins comprising the present invention.

The present invention provides a recombinant immune cell and the preparation method, the gene regulation system and the use thereof. By reducing or eliminating the expression and/or biological functions thereof of the BCOR gene and the ZC3H12A gene, the persistence of the recombinant immune cell is enhanced. In some embodiments, the present invention obtains CAR-T cells with knockout of double genes ZC3H12A and BCOR by gene editing, which can persist in vivo, solving the technical problem of long-term effectiveness of CAR-T treatment. In some embodiments, the gene-edited CAR-T cells persist in vivo and can continuously secrete therapeutic biological molecules, achieving the purpose of long-term effectiveness of a single administration.

The invention comprises methods and compositions for treating autoimmune diseases with engineered immune cells including cytotoxic T cells and natural killer (NK) cells. The engineered immune cells comprise a chimeric antigen receptor (CAR). Methods of making the engineered cells, methods of administration and treatment regimens are also disclosed.

Compositions and methods for modulation by upregulation (up modulation) and/or downregulation (down modulation) of mitophagy are described for the treatment of mitochondrial disorders including OPA-1 related disease and Single Large Scale Mitochondrial DNA Deletion (SLSMD). Also disclosed are a number of screening assays and gene targets having utility for the identification of agents which modulate the phenotype associated with such disorders.

Methods and compositions are provided for using transcription start site (TSS) profiling to identify alternate promoters that yield better transcription modulation (e.g., knockdown using CRISPRi or activation using CRISPRa). Methods can also include designing CRISPR-Cas guide RNAs to target CRISPRi or CRISPRa complexes to the identified alternative promoters, and methods can also include steps of generating such guide RNAs. Also provided are libraries of guide RNA, methods of modulating expression of a target gene. In some cases, multiple promoters for the same gene are targeted simultaneously.

Compositions of aCap virus-ribonucleic acid protein complex conjugates (VRC), wherein a viral capsid protein is covalently linked to a ribonucleic acid protein complex, i.e., a ribonucleoprotein (RNP), for selective delivery of the RNP into a targeted cell nucleus, and their preparation and uses as therapeutics.

CRISPR-Cas systems have been engineered for various purposes, such as genomic DNA cleavage, base editing, epigenome editing, and genomic imaging. Although significant developments have been made, there still remains a need for new and useful CRISPR-Cas systems as powerful precise genome targeting tools. The invention disclosed herein comprises CRISPR-Cas based methods for high integration and expression efficiency of transgenes together with high post-transfection cell viability in eukaryotic cells.

Disclosed herein are methods of enhancing extracellular vesicle production.