The invention provides a method of modifying a targeted site of a double stranded DNA, including a step of contacting a complex wherein a nucleic acid sequence-recognizing module that specifically binds to a target nucleotide sequence in a selected double stranded DNA and a nucleic acid base converting enzyme are linked, with the double stranded DNA, to convert one or more nucleotides in the targeted site to other one or more nucleotides or delete one or more nucleotides, or insert one or more nucleotides into the targeted site, without cleaving at least one strand of the double stranded DNA in the targeted site.

Disclosed herein are methods and compositions for targeted cleavage of a genomic sequence, targeted alteration of a genomic sequence, and targeted recombination between a genomic region and an exogenous polynucleotide homologous to the genomic region. The compositions include fusion proteins comprising a cleavage domain (or cleavage half-domain) and an engineered zinc finger domain and polynucleotides encoding same. Methods for targeted cleavage include introduction of such fusion proteins, or polynucleotides encoding same, into a cell. Methods for targeted recombination additionally include introduction of an exogenous polynucleotide homologous to a genomic region into cells comprising the disclosed fusion proteins.

The present disclosure provides zinc finger fusion proteins that inhibit expression of tau in the nervous system, and methods of using the proteins to treat neurodegenerative diseases such as Alzheimer's disease, frontotemporal dementia, and other tauopathies.

The present disclosure provides danoprevir/NS3a complex reader (DNCR) and grazoprevir/NS3a complex readers (GNCR) polypeptides, fusion proteins, and combinations and their use.

A protein having a binding ability to guide RNA and consisting of a sequence containing an amino acid sequence wherein a continuous deletion region is present between the 481-position and the 649-position in the amino acid sequence shown in SEQ ID NO: 2, the deletion region containing

(i) all or a part of L1 domain (481- to 519-positions), and
(ii) entire HNH domain (520- to 628-positions), and further optionally containing
(iii) all or a part of L2 domain (629- to 649-positions), wherein amino acids adjacent to each of the deletion region are linked by a linker consisting of 3 to 10 amino acid residues functions as a miniaturized dSaCas9 protein while maintaining DNA binding affinity. Use of the miniaturized dSaCas9 protein makes it possible to mount many genes into vectors.

The present disclosure is in the field of genome engineering, particularly targeted modification of the genome of a hematopoietic cell.

Tunneling nanotube (TNT) cells, comprising a TNT promoting factor (TPF); and a biomolecule cargo overexpressed by the TNT cell, and methods of use thereof for delivery of the biomolecule cargo from TNT cells to neighboring cells.

The present disclosure relates to recombinant nucleases, recombinant nucleases operatively linked to nucleic acid binding domains, and methods of making and using them.

The technology described herein is directed to compositions comprising components of multi-component CALs or CARs, e.g., a TCR recognition domain; and one or both of: (a) an intracellular signaling domain; and (b) a first-type protein interaction domain. Further provided herein are methods for treating or preventing an autoimmune disease, a transplant rejection, or graft versus host disease.

Embodiments disclosed herein provide artificial expression systems comprising multivalent transcription factor complexes for cooperative transcription factor assembly and modulating gene expression. More specifically, engineered synthetic transcription factors are recruited and structurally organized on synthetic gene circuits using molecular clamps, where the strength of intra-complex interactions can be modulated for fine tuning of gene expression as desired.