The present disclosure provides adenine base editors (ABEs) that are variants of known adenine base editors. The adenosine deaminase domain of a known ABE was modified to produce adenosine deaminase variants. The deaminase variants provided herein have broader compatibility with diverse napDNAbp domains, such as Cas homologs, for base editing applications. The ABEs provided herein comprise a deaminase variant and a napDNAbp domain. The ABEs provided herein exhibit reduced off-target editing effects while retaining high on-target editing efficiencies. These ABEs exhibit reduced off-target DNA editing effects and reduced off-target editing effects in cellular mRNA. In addition, methods for targeted nucleic acid editing are provided. Further provided are pharmaceutical compositions comprising the ABEs. Also provided are vectors and kits useful for the generation and delivery of the ABEs, including vector systems for engineering the ABEs through directed evolution. Cells containing such vectors and ABEs are also provided. Further provided are methods of treatment comprising administering the ABEs.

A method for producing genetically engineered immune cells, e.g. T cells, or iPSCs which uses an RNA-scaffold mediated base editing system. The method enables precise modifications to be made to the genome whilst minimizing the possibility of off-target effects, making the method particularly suitable for therapeutic applications.

The present invention belongs to the field of genetic engineering. Specifically, the present invention relates to a gene editing system derived from Flavobacterium and uses thereof.

The current invention provides methods of combinatorial genetic screening in a cancer cell comprising an enhanced CRISPR-Cas12a system, and compositions comprising the same. Also provided are methods for screening for synergistic combinations of drug targets, as well as the treatment of cancer in a subject in need thereof.

The present invention relates a vector system and a vector system for use in a method of treating a disease, each comprising a first vector and a second vector. The present invention further relates to the first vector, the second vector and a combination of the first vector and the second vector. In addition, the present invention relates to a pharmaceutical composition comprising the vector system of the invention or the combination of the invention.

Provided herein are compositions and methods for improving the genome-wide specificities of targeted base editing technologies.

The present disclosure provides RNA-guided CRISPR-Cas effector proteins, nucleic acids encoding same, and compositions comprising same. The present disclosure provides ribonucleoprotein complexes comprising: an RNA-guided CRISPR-Cas effector protein of the present disclosure; and a guide RNA. The present disclosure provides methods of modifying a target nucleic acid, using an RNA-guided CRISPR-Cas effector protein of the present disclosure and a guide RNA.

A Class 2, Type VI clustered regularly interspaced short palindromic repeat (CRISPR) RNA (crRNA) which comprises a direct repeat (DR) stem loop sequence and a guide or spacer sequence, is provided characterized by a DR selected from those of Table 9. Also described is are methods for generating, selecting, characterizing and optimizing a clustered regularly interspaced short palindromic repeats (CRISPR) RNA (crRNA) for use in the CRISPR-Cas13d system described herein. Also provided is a screening method to identify crRNA particularly suited for use with specified targets. Further, the invention includes non-naturally occurring, synthesized or engineered crRNAs as described herein along with nucleic acid molecule, vectors, RNPs, cells, libraries, and compositions comprising the same, and uses thereof in treating a disease or in functionally screening a gene. A method for blocking an RNA target without degradation and a method for modification of multiple RNA targets using the same CRISPR effector protein are also disclosed.

Agents having cytotoxic activity, as well as compositions, uses, and methods relating thereto, are described herein. Certain steroid acid-peptide conjugates or moieties have the ability to induce killing or inhibition of proliferation of mammalian cells, in vitro or in vivo upon administration to a subject. The steroid acid-peptide conjugates include bile acids and bile acid analogs and peptides that may include a nuclear localisation signal or a portion thereof. Also described herein is a method for treating cancer, an autoimmune disease, or any other disease or disorder ameliorated by treatment with an antiproliferative drug in a subject in a subject with the cytotoxic agents described herein.

The present invention belongs to the field of plant genetic engineering. Specifically, the invention relates to a method for base editing in plants. More particularly, the invention relates to a method for performing efficient base editing to a target sequence in the genome of a plant (such as a crop plant) by a Cas9-cytidine deaminase fusion protein, as well as plants produced through said method and progenies thereof.