Systems, methods and composition for targeting polynucleotides are detailed herein. In particular, engineered DNA-targeting systems comprising novel Fanzor polypeptides and a reprogrammable targeting nucleic acid component and methods and application of use are provided.

The disclosure provides, e.g., compositions, systems, and methods for targeting, editing, modifying, or manipulating a host cell's genome at one or more locations in a DNA sequence in a cell, tissue, or subject.

Compositions and methods for editing, e.g., altering a DNA sequence, within a CD38 gene are provided. Compositions and methods for immunotherapy are provided.

Disclosed are recombinant virions that have a capsid protein or a variant thereof of erythroparvovirus and a nucleic acid that includes a heterologous nucleic acid.

The present invention provides methods of increasing plant productivity and tolerance to water and nutrient deficiency by overexpressing an exonuclease responsible for the d200 mutant. Also provided are plants which overexpress the exonuclease and have improved tolerance to water and nutrient deficiency.

Provided herein are polynucleotides and CRISPR effector proteins configured to be covalently bound together in a CRISPR complex. The polynucleotides can be further modified to modulate the activity of the CRISPR complex. Modification of the polynucleotide and CRISPR effector protein can be used to improve the efficacy of target binding and/or cleavage.

An immune cell with down-regulated cell adhesion capability and the medical use thereof. The immune cell is a tumor killer cell for adoptive immune cell therapy, and has down-regulated cell adhesion capability. The immune cell has better safety for hematological tumors and solid tumors.

Provided herein are methods of producing a composition comprising genetically engineered cells for cell therapy, the method comprising: selecting one or more genetically engineered cells from a population of cells, and formulating the composition comprising the selected one or more genetically engineered cells for use, wherein the one or more genetically engineered cells comprise one or more genetic modifications, and wherein the one or more genetically engineered cells are selected based on a level of one or more markers on the cell surface of the one or more genetically engineered cells, as well as compositions derived therefrom.

The application provides modified immune effector cells wherein a Lysine Demethylase 4A (KDM4A) gene or gene product is modified in the cell so that the expression and/or function of KDM4A in the cell is reduced or eliminated. The application also provides related pharmaceutical compositions and the methods for generating such modified immune effector cells. The application further provides uses of such modified immune effector cells for treating diseases such as cancers, infectious diseases and autoimmune diseases.

Provided herein are AAV capsid polypeptides comprising peptide modifications relative to the wild-type AAV6 polypeptide that, when present in the capsid of an AAV vector, can facilitate homology directed repair (HDR)-mediated gene editing of human T cells. Also provided are AAV vectors comprising the capsid polypeptides, nucleic acid vectors comprising the encoding nucleic acid molecules, and host cells comprising the vectors, as well as methods of use of such AAV vectors, nucleic acid vectors and host cells.