The invention features compositions and methods for editing a transthyretin polynucleotide sequence to treat amyloidosis.

Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins of Cas9 and nucleic acid editing enzymes or enzyme domains, e.g., deaminase domains, are provided. In some embodiments, methods for targeted nucleic acid editing are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of Cas9 and nucleic acid editing enzymes or domains, are provided.

The present invention relates to therapeutic cells for immunotherapy to treat patients with cancer. In particular, the inventors develop a method of engineering prodrug-specific hypersensitive T-cell, which can be depleted in vivo by the administration of said specific prodrug in case of occurrence of a serious adverse event. The invention opens the way to safer and tunable adoptive immunotherapy strategies for treating cancer.

The present invention relates to an oncolytic virus encoding a cytidine deaminase (CDAse) polypeptide, a composition comprising it, as well as their use for prophylactic or therapeutic purposes, and more particularly for the treatment of cancer. The present invention also provides a method for treating a disease or a pathologic condition comprising the administration of such an oncolytic virus or composition thereof and a process for preparing such an oncolytic virus.

Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins of Cas9 and nucleic acid editing enzymes or enzyme domains, e.g., deaminase domains, are provided. In some embodiments, methods for targeted nucleic acid editing are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of Cas9 and nucleic acid editing enzymes or domains, are provided.

Provided herein is technology relating to the mutagenesis of nucleic acids, e.g., for directed evolution, and particularly, but not exclusively, to methods, compositions, and kits for producing nucleic acids and/or proteins comprising mutations and substitutions within specific target sequences.

Disclosed herein are methodologies and kits for dynamic targeted hypermutation that harness the enzymatic activity of a polynucleic acid-binding protein fused to a nucleobase-editing enzyme to specifically target mutations across a region of interest. These methodologies and kits facilitate the rapid creation of diverse DNA libraries in vivo or in vitro.

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.

The present invention provides novel systems, methods and compositions for making and using recombinantly engineered novel Cas9 enzymes optimized for human cells, for nucleic acid targeting and manipulation. The present invention is based on the discovery of novel Cas9 enzymes from Streptococcus constellatus, Sharpen spp. isolate RUG017, Veillonella parvula, Ezakiella peruensis, Lactobacillus fermentum strain AF15-40LB strain and Peptoniphilus sp. Marseille-P3761 bacteria that were codon-optimized and recombinantly produced for use in human cells. In some embodiments, novel Cas9 enzymes can be used for base editing. In some embodiments, the novel engineered Cas9 enzymes are used to treat human diseases.

Methods and compositions for performing highly sensitive in vitro assays to define substrate preferences and off-target sites of nucleic-acid binding, modifying, and cleaving agents.