Abstract: Provided herein are gRNA comprising a targeting domain that targets EMR2, which may be used, for example, to make modifications in cells. Also provided herein are methods of genetically engineered cell having a modification (e.g., insertion or deletion) in the EMR2 gene and methods involving administering such genetically engineered cells to a subject, such as a subject having a hematopoietic malignancy.

Abstract: 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.

Abstract: This disclosure provides, inter alia, genetically engineered cells having an artificial protospacer-adjacent motif (PAM) introduced via a CRISPR/Cas-mediated gene editing, and optionally, one or more modifications in a target gene. The disclosure also provides methods and compositions, including gRNAs, that can be used to make such modifications.

Abstract: Provided herein are compositions and methods for genetically engineering a cell (e.g., a hematopoietic cell) to modify a gene encoding a lineage-specific cell-surface antigen to modify an epitope of the lineage-specific cell-surface antigen recognized by an agent. Also provided are methods involving administering such genetically engineered cells to a subject, such as a subject having a hematopoietic malignancy, as well as the genetically engineered cells themselves.

Abstract: Provided herein are methods and compositions for genetically engineering a cell (e.g., a hematopoietic cell) using CRISPR/Cas systems and homology-directed repair, genetically engineered cells produced by such methods, and methods involving administering such genetically engineered cells to a subject, such as a subject having a genetic disease.

Abstract: 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.

Abstract: When a cancer patient is administered an anti-cancer therapy targeting a lineage specific cell-surface antigen (e.g., CD33 (Siglec-3), CLL-1, CD123, CD327 (Siglec-6), and/or CD312 (EMR2)), e.g., in the form of an immunotherapeutic agent, the therapy can deplete not only cancer cells expressing the lineage-specific cell-surface antigen, but also noncancerous cells expressing the lineage-specific cell-surface antigen in an “on-target, off tumor” effect. This disclosure provides, e.g., novel cells having a modification (e.g., insertion or deletion) in an endogenous lineage-specific cell-surface antigen (e.g., CD33 (Siglec-3), CLL-1, CD123, CD327 (Siglec-6), and/or CD312 (EMR2)) gene. The disclosure also provides compositions, e.g., gRNAs, that can be used to make such a modification.

Abstract: Disclosed herein are compositions, methods, and kits for use in treating hematopoietic malignancies, the compositions, methods, and kits comprise a cytotoxic agent targeting cells expressing a lineage-specific cell-surface protein and a population of hematopoietic cells that express the lineage-specific cell-surface protein, the hematopoietic cells being manipulated such that they do not bind the cytotoxic agent.

Abstract: Provided herein are gRNA comprising a targeting domain that targets BCMA, which may be used, for example, to make modifications in cells. Also provided herein are methods of genetically engineered cell having a modification (e.g., insertion or deletion) in the BCMA gene and methods involving administering such genetically engineered cells to a subject, such as a subject having a hematopoietic malignancy.

Abstract: This disclosure provides, e.g., novel cells having a modification (e.g., insertion or deletion) in the endogenous CD 123 gene. The disclosure also provides compositions, e.g., gRNAs, that can be used to make such a modification.

Abstract: Disclosed herein are compositions, methods, and kits for use in treating hematopoietic malignancies, the compositions, methods, and kits comprise a cytotoxic agent targeting cells expressing a lineage-specific cell-surface protein and a population of hematopoietic cells that express the lineage-specific cell-surface protein, the hematopoietic cells being manipulated such that they do not bind the cytotoxic agent.

Abstract: This disclosure provides, e.g., novel cells having a modification (e.g., insertion or deletion) in the endogenous CLL1 gene. The disclosure also provides compositions, e.g., gRNAs, that can be used to make such a modification.

Abstract: 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.

Abstract: Provided herein are gRNA comprising a targeting domain that targets CD5, which may be used, for example, to make modifications in cells. Also provided herein are methods of genetically engineered cell having a modification (e.g., insertion or deletion) in the CD5 gene and methods involving administering such genetically engineered cells to a subject, such as a subject having a hematopoietic malignancy.

Abstract: Provided herein are gRNA comprising a targeting domain that targets CD7, which may be used, for example, to make modifications in cells. Also provided herein are methods of genetically engineered cell having a modification (e.g., insertion or deletion) in the CD7 gene and methods involving administering such genetically engineered cells to a subject, such as a subject having a hematopoietic malignancy.

Abstract: Aspects of the disclosure provide methods and compositions for treating a hematopoietic malignancy (e.g., acute myeloid leukemia). In some aspects, the disclosure provides methods of treatment using a population of genetically engineered CD33-deficient hematopoietic cells and a cytotoxic agent comprising an anti-CD33 antigen-binding domain.

Abstract: Provided herein are gRNA comprising a targeting domain that targets CD38, which may be used, for example, to make modifications in cells. Also provided herein are methods of genetically engineered cell having a modification (e.g., insertion or deletion) in the CD38 gene and methods involving administering such genetically engineered cells to a subject, such as a subject having a hematopoietic malignancy.

Abstract: Provided herein are gRNA comprising a targeting domain that targets CD30, which may be used, for example, to make modifications in cells. Also provided herein are methods of genetically engineered cell having a modification (e.g., insertion or deletion) in the CD30 gene and methods involving administering such genetically engineered cells to a subject, such as a subject having a hematopoietic malignancy.

Abstract: Provided herein are gRNA comprising a targeting domain that targets CD6, which may be used, for example, to make modifications in cells. Also provided herein are methods of genetically engineered cell having a modification (e.g., insertion or deletion) in the CD6 gene and methods involving administering such genetically engineered cells to a subject, such as a subject having a hematopoietic malignancy.

Abstract: 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.