Methods and compositions for modifying the expression of endogenous genes or modifying the coding sequence of endogenous genes.

This application provides improved methods of editing the genome of a target cell. Cas9 molecules can be used to create a break in a genomic region of interest. To increase the likelihood that the break is repaired by homology-directed repair (HDR), the cell can be contacted with an HDR-enhancer. The cell may be, e.g., a human cell, a non-human animal cell, a bacterial cell, or a plant cell.

The present disclosure is broadly concerned with the field of cancer immunotherapy. For example, the present invention generally relates to an immune cell comprising a genetically engineered antigen receptor that specifically binds to a target antigen and a genetic disruption agent that reduces or is capable of reducing the expression in the immune cell of a gene that weakens the function of the immune cell.

The invention relates to plants have a nucleus-encoded, recessive, male sterile phenotype and to the gene locus (gsf) correlating therewith, including the gene which is responsible for the fertile/sterile phenotype and which is mutated in the sterile phenotype. The invention further provides methods for identifying the genotype correlating with the expression of features the plants obtained accordingly to the invention in hybrid breeding and in the production of products obtained from renewable raw materials, such as bioethanol, biogas and sugar-based products.

The present disclosure relates to methods for transiently activating temperature-sensitive agents in one or more cells, for example by contacting one or more cells with a temperature-sensitive agent and transiently incubating the cells at a permissive temperature for inducing an activity of the temperature-sensitive agent in the cells. Additionally, the present disclosure relates to methods of contacting one or more cells in a subject with a temperature-sensitive agent and then lowering the subject's core body temperature to a permissive temperature for inducing an activity of the temperature-sensitive agent in the cells. The disclosure also relates to methods of contacting one or more cells in a subject with a temperature-sensitive agent, maintaining the subject's surface body temperature at a permissive temperature for inducing an activity of the temperature-sensitive agent in the cells. Further disclosed are methods of treating a subject with a temperature-sensitive therapeutic agent.

Disclosed is an adaptor for sequencing DNAs at ultratrace levels and its uses. The adaptor contains, from 5′terminus to 3′terminus, a Tag sequence, PolyNs, a first stem sequencing, a first loop sequence, dUTP(s), a second loop sequence, and a second stem sequence, wherein the second stem sequence is complementary to the first stem sequence when read in opposite directions, and the 5′terminus of the adaptor is phosphorylated. The adaptor is designed to form a hairpin structure itself in use and then ligated to a DNA molecule of interest, so that adaptor-adaptor ligation can be effectively avoided, eliminating the inefficient adaptor-DNA ligation problem. Such an adaptor is especially suitable for library construction and sequencing of DNAs at ultratrace levels, laying a good basis for accurate sequencing of ctDNAs.

Disclosed herein are methods of inhibiting nuclear pore complex assembly and inducing nuclear pore complex disassembly. Methods to screen for agents that inhibit nuclear pore assembly or induce nuclear pore complex disassembly are also disclosed.

The present disclosure provides methods and compositions related to the modification of immune effector cells to increase therapeutic efficacy. In some embodiments, immune effector cells modified to reduce expression of one or more endogenous target genes, or to reduce one or more functions of an endogenous protein to enhance effector functions of the immune cells are provided. In some embodiments, immune effector cells further modified by introduction of transgenes conferring antigen specificity, such as exogenous T cell receptors (TCRs) or chimeric antigen receptors (CARs) are provided. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.

The present disclosure provides, in some aspects, nucleic acid-based molecular tools that enable the recording of molecular structure and soluble signals as well as the programmed assembly of molecular structures.

Modulators of intracellular chloride concentration for treating down syndrome The present invention relates to a modulator of a chloride transporter for use in the treatment of Down syndrome.