Beam Therapeutics Inc.

Compositions and methods for treating phenylketonuria by introducing one or more alterations into a phenylalanine hydroxylase (PAH) polynucleotide in a cell. In particular embodiments, the disclosure provides a base editor system (e.g., a fusion protein or complex comprising a programable DNA binding protein, a nucleobase editor, and gRNA) for modifying a PAH polynucleotide, where the alteration is associated with an increase in the level or activity of a PAH polypeptide encoded by the polynucleotide.

The disclosure features compositions and methods for treating cardiovascular disease by introducing one or more alterations into a lipoprotein(a) (LPA) polynucleotide in a cell. In particular embodiments, the disclosure provides a base editor system (e.g., a fusion protein or complex comprising a programable DNA binding protein, a nucleobase editor, and gRNA) for modifying an LPA polynucleotide, where the modification is associated with reduced expression, and/or reduced activity of the LPA polypeptide encoded by the polynucleotide.

As described below, the present disclosure features modified immune effector cells (e.g., T or NK cells) having increased resistance to inhibition by immunosuppressant agents relative to unmodified immune effector cells, compositions containing the same, and methods for use thereof.

The present invention features genetically modified immune cells comprising novel adenosine base editors (e.g., ABE8) having enhanced anti-neoplasia activity, resistance to immune suppression, and decreased risk of eliciting a graft-versus-host reaction or host-versus-graft reaction, or a combination thereof. The present invention also features methods for producing and using these modified immune effector cells.

The invention provides compositions and methods for delivering first and second polynucleotides each encoding a fragment of an A-to-G Base Editor fusion protein comprising one or more deaminases (e.g., adenosine deaminases) and nCas9, wherein the first polynucleotide encodes an N-terminal fragment of nCas9 fused to an intein-N of a split intein pair and the second polynucleotide encodes a C-terminal fragment of nCas9 fused to an intein-C of a split intein pair, and methods for delivering these fragments together with an sgRNA to a cell (e.g., AAV delivery), where the fragments are spliced together by a split intein system, thereby reconstituting a functional base editing system in the cell.

The present disclosure describes compositions, preparations, nanoparticles (such as lipid nanoparticles), and/or nanomaterials and methods of their use, including compounds of Formula (I) or a pharmaceutically acceptable salt thereof.

The present disclosure describes compositions, preparations, nanoparticles (such as lipid nanoparticles), and/or nanomaterials and methods of their use such as a compound of Formula (A) or a pharmaceutically acceptable salt thereof.

Compositions and methods for non-genotoxic monoclonal antibody (mAb) conditioning, where the methods involve altering a cluster of differentiation 117 (CD117; c-KIT) polynucleotide sequence in a hematopoietic stem cell (HSC) or progenitor thereof to encode a CD117 polypeptide with reduced binding to the antibody. In various embodiments, the methods further include introducing a therapeutic alteration to a gene of the HSC or progenitor thereof for treatment of a hemoglobinopathy.

As described below, the present disclosure features polypeptides capable of binding a cluster of differentiation 5 (CD5) antigen and polynucleotides encoding said CD5-binding polypeptides, compositions comprising the same, and methods for use thereof. The disclosure also features lipid nanoparticles comprising the CD5-binding polypeptides and methods for use thereof for delivery of a polynucleotide (e.g., a polynucleotide encoding a chimeric antigen receptor) to a T cell in vivo.

Compositions and methods for editing deleterious mutations associated with Alpha-1 Antitrypsin Deficiency (A1AD). In particular embodiments, the invention provides methods for treating A1AD using a modified adenosine base editor with improved on-target editing and decreased off-target editing to correct mutations associated with A1AD.