The present disclosure is directed to DNA-PK inhibitors having the Formula (I),

##STR00001##

or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof, methods of preparing the foregoing, and compositions thereof, as well as methods of use for the compounds of Formula (I), in combination with a DNA cutting agent.

A method of treating or inhibiting a viral infection in a human subject, such as a SARS-CoV-2 infection, involves inhibiting in vivo the expression or activity of one or a combination of the subject's genes required for viral infection. Single genes or subsets of genes for inhibition of activity or expression are selected from certain identified genes. Methods of administration of certain known small molecules or other therapeutics which mimic loss of function of the identified genes are provided. Similar methods for conducting screens of host genes required for viral infection are shown.

The present disclosure is directed to genetically modified cells that express one or more transgenes at a sustained expression level from a site for safe genomic integration and stable expression. Also provided are methods of making the cells and nucleic acid vectors that can be used to make the cells.

The present invention relates to a vector suitable for a targeted integration of at least one gene of interest in 5 or 3 of a polyubiquitin gene in a plant. The present invention also relates to the use of said vector in a method for targeted insertion of at least one gene of interest in a plant genome and to a plant cell or plant tissue obtained by transformation with said vector. The present invention further relates to a method of identifying a plant having at least one gene of interest inserted in 5 or 3 of a polyubiquitin gene.

The present disclosure provides compositions and methods for treating and preventing localized nociception, inflammation, or morphological changes associated with joint disease or illness, back or spine conditions or disorders, and musculoskeletal diseases or dysfunction with an LNP-encapsulated CRISPR/Cas9 gene editing system.

The disclosure relates to compositions comprising and methods of administration to a mammal of single guide RNA (sgRNA), tracrRNA and/or crRNA used individually or in combination with one another or Cas system components in order to treat African Swine Fever Virus (ASFV). The disclosure also relates to systems for assaying therapeutically effective amounts of nucleic acid and protein that inhibit ASFV replication. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

Compositions and methods for reducing MHC class I protein expression in a cell comprising genetically modifying MHC class I for use e.g., in adoptive cell transfer therapies.

Disclosed herein are effector domains. The effector domains may be used with, for example, Cas proteins and CRISPR-Cas systems. The effectors may be used in combination with a Cas protein to form a fusion protein. The effectors may also be used in combination with an antibody that binds to a peptide epitope, wherein the peptide epitope is fused to a Cas protein. The compositions and methods comprising the effectors may be used to modulate gene expression.

The disclosure relates to novel plants, plant parts, and nucleotide sequences in soybean plants comprising a mutated JAG1 gene, along with methods of using and making the same. Wherein the mutated JAG1 gene comprises a null mutation in the JAG1 gene encoding the polypeptide of SEQ ID NO: 10 or an allelic variant thereof and wherein the soybean plant cell lacks a loss-of-function mutation in the soybean JAG2 gene.

This invention provides guide RNA (gRNA) constructs designed to enhance safety and precision in therapeutic gene editing across RNA-guided systems. The constructs incorporate a non-nucleotide linker near the middle of the spacer sequence, reducing truncated spacer impurities (e.g., n1 variants) during production by ligating short RNA segments (e.g., 10 nt and 22 nt)minimizing off-target risks in gene editing therapies. Additionally, a DNA restriction enzyme cleavage site near the spacer's internal end enables excision of a short RNA fragment (e.g., 32 nt for spCas9) for precise spacer purity analysis via LC-MS or electrophoresis. These features ensure robust GMP production and quality control, overcoming limitations of conventional gRNAs and long RNAs (>160 nt) used in diverse editing platforms. Applicable to CRISPR-based and other RNA-guided methods, the constructs maintain or enhance activity, offering a scalable, safe solution for therapeutic gene editing.