Genetically engineered hematopoietic cells such as hematopoietic stem cells having one or more genetically edited genes of lineage-specific cell-surface proteins and therapeutic uses thereof, either alone or in combination with immune therapy that targets the lineage-specific cell-surface proteins.

The present disclosure provides 2-in-1 zinc finger nuclease variants and methods of treating and/or preventing a lysosomal storage disorder using said zinc finger nuclease variants.

Systems and methods for targeted gene modification, targeted insertion, perturbation of gene transcripts, and nucleic acid editing. Novel nucleic acid targeting systems comprise components of CRISPR systems, reverse transcriptase, pegRNAs, paired pegRNAs or modified pegRNAs, DNA processing proteins, recombinases, proteins for inhibiting nucleases, and proteins for promoting ssDNA annealing.

Systems and methods for targeted gene modification, targeted insertion, perturbation of gene transcripts, and nucleic acid editing. Novel nucleic acid targeting systems comprise components of CRISPR systems, reverse transcriptase, pegRNAs, paired pegRNAs or modified pegRNAs, DNA processing proteins, recombinases, proteins for inhibiting nucleases, and proteins for promoting ssDNA annealing.

The present application relates to a method of recombinantly engineering a Leishmania cell that involves homologous recombination of DNA fragments. Further provided herein are Leishmania cells recombinantly engineered using the method provided herein. Also provided herein are methods of making a polypeptide using a Leishmania cell described herein and polypeptides produced by the methods provided herein.

The present disclosure generally relates to therapies involving immune effector cells such as T cells engineered to express antigen receptors such as T cell receptors (TCRs) or chimeric antigen receptors (CARs). It is demonstrated herein that such antigen receptor-engineered immune effector cells may be generated in vitro/ex vivo as well as in vitro by delivering nucleic acid encoding an antigen receptor for genetic modification to cells using particles comprising the nucleic acid and a targeting molecule for targeting the immune effector cells, wherein the targeting molecule is a designed ankyrin repeat protein (DARPin). In particular, DARPins are described herein which are high-affinity binders for CDS binding to the CDS receptor on human and non-human primate (NHP) cells. Nanoparticles functionalized with CD8− targeting DARPins (CDS-DARPin) can deliver genes exclusively and specifically to human CD8.sup.+ T cells in vitro and in vivo.

Disclosed are cells that have stably integrated into their genomes exogenous nucleic acid sequences, such as transgenes, within or proximal to the integration site of a sequence comprising at least part of an endogenous retrovirus (ERV) or a LTR-retrotransposon (LTR-RT), or instead of a sequence encompassing an ERV or a LTR-RT that is part or was part of the genome of the cell, as well as method of producing and using such cells. Advantageously, a high level and/or stable production of the transgene expression product(s) can be achieved. Transgene integration and expression may be furthered by modulating the DNA repair pathways of the cell, e.g., by transiently expressing a gene encoding a protein that forms part of a DNA repair pathway during transgene integration.

The invention relates to logic-gate-based Type II or Type V CRISPR-Cas constructs and methods for modifying gene expression using the CRISPR-Cas constructs and CRISPR-Cas effector proteins.

The disclosure is directed to compositions and methods comprising genetically engineered fibroblasts for inhibiting progression of a cancerous tumor.

RNA-guided programmable cytosine and adenine base editors are a powerful class of genome editing tool for the introduction of localized base transitions without generating a double-stranded DNA break. Base editors (BE) have an optimal window of activity relative to the PAM recognized by the Cas9 enzyme and these constructs are strand selective. Here we demonstrate that fusion of a programmable DNA-binding domain (pDBD) or another Cas9 orthologue to spCas9-BE, we can produce an RNA-programmable Cas9-BE-pDBD chimera or Cas9-BE-Cas9 chimeras with dramatically improved activities and increased targeting range. Cas9-pDBD or Cas9-Cas9 fusion base editors display an expanded targeting repertoire and achieve highly specific genome editing, which can be tailored to achieve extremely precise genome editing at nearly any genomic locus.