The present invention aims to provide a novel therapeutic approach to human muscular dystrophy (particularly MDC1A). The present invention provide a polynucleotide comprising the following base sequences: (a) a base sequence encoding a fusion protein of a nuclease-deficient CRISPR effector protein and a transcription activator, and (b) abase sequence encoding (i) a guide RNA targeting continuous region set forth in SEQ ID NO: 15, 20, 25, 50, 56, or 61, (ii) a guide RNA targeting a continuous region set forth in SEQ ID NO: 124, or (iii) a guide RNA targeting a continuous region set forth in SEQ ID NO: 178, 193, or 195, in the expression regulatory region of human LAMA1 gene.

Provided herein are polynucleotides, lentiviral vectors, pharmaceutical compositions, and methods of making and using the same, e.g., for treatment of cystic fibrosis (CF).

Disclosed herein are engineered guide RNAs, engineered polynucleotides, precursor engineered polynucleotide, vectors omprising engineered polynucleotide, nucleic acids of engineered polynucleotide, pharmaceutical compositions thereof, methods of making the engineered polynucleotides and methods of treating or preventing a disease or condition by administering above described thereof.

Described herein are systems for targeting viral genomes. Also described herein are methods for targeting viral genomes utilizing the systems described in the instant disclosure. In some cases, systems and methods disclosed herein can be used to treat viral infections. In preferred embodiments, the systems utilise a CRISPR/Cas13d complex to target the genome of an RNA virus such as coronavirus or influenza virus.

The present invention provides an anti-CD22 antibody molecule and a CD22-targeted chimeric antigen receptor (CAR) constructed using the anti-CD22 antibody molecule. The present invention also provides an application of the anti-CD22 antibody molecule and the CAR in the preparation of drugs for treating CD22-related diseases.

The present disclosure generally relates to, inter alia, a new class of chimeric Notch receptors containing a synthetic zinc finger transcriptional effector (synZTE) module, engineered to modulate gene expression and cellular activities in a ligand-dependent manner. The new Notch receptors surprisingly retain the ability to transduce signals in response to ligand binding despite that the Notch extracellular subunit (NEC), which includes the negative regulatory region (NRR) previously believed to be essential for the functioning of Notch receptors, is partly or completely deleted. In addition, the synZTE is designed to bind orthogonal DNA target sequences in target organisms which in turn facilitates precise regulation of therapeutic gene expression with minimal off-target activity. Also provided are compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various health conditions such as cancers.

The invention provides a medication and a diagnostic kit for inhibiting metastasis and invasion of breast cancer, an shRNA molecule for silencing expression of human LINC01614 and applications thereof. The shRNAs obtained by the invention can interfere with the expression of LINC01614, thereby reducing the migration and invasion ability of tumor cells, inhibiting the expression of EMT proteins, and inhibiting tumor formation and lung metastasis in an animal model in vivo. The invention provides a new solution for targeted therapy of breast cancer. Therefore, the kit for diagnosing metastasis and invasion of breast cancer and the medication for treating metastasis and invasion of breast cancer are developed. The invention provides a new way and strategy for diagnosing and treating metastasis and invasion of breast cancer.

The present invention refers to a method to produce a T cell with advantageous properties. The invention also refers to a T cell or an engineered T cell produced by the method and its use in therapy.

Embodiments of the disclosure include methods and compositions for in situ cardiac cell regeneration, including transdifferentiation of cardiac cells to cardiomyocytes. In particular embodiments, in situ cardiac cell regeneration encompasses delivery of p63 shRNA and one or both of Hand2 and myocardin, and in specific embodiments further includes one or more of Gata4, Mef2c, and Tbx5. In specific aspects of the disclosure, adult cardiac fibroblasts are reprogrammed into cardiomyocytes using viral vectors that harbor p63 shRNA and one or both of the transcription factors Hand2 and myocardin.

A lentiviral vector production system comprises (a) a lentiviral culture supplement to control cell growth, (b) a transfection reagent comprising DHDMS, DOPE, and cholesterol to increase transfection efficiency, (c) a lentiviral production enhancer comprising sodium propionate, sodium butyrate, and caffeine to boost lentiviral production, wherein the lentiviral vector production system is serum-free. A method of lentiviral vector production comprises using the lentiviral production system. Another method for lentiviral vector production comprises (a) culturing eukaryotic cells in a serum-free medium, (b) providing a lentiviral culture supplement to control cell growth, (c) transfecting the cells with a lentiviral vector using a transfection reagent comprising DHDMS, DOPE, and cholesterol to increase transfection efficiency, and (d) providing a lentiviral production using a lentiviral production enhancer comprising sodium propionate, sodium butyrate capable of boosting lentiviral production.