Sana Biotechnology, Inc.

Methods of profiling cells for donor capability with a recipient subject are provided. In particular, methods relating to identifying cells, such as T cells, suitable for making a cell therapy product and administration to a patient (e.g., as CAR T cell therapy). Methods are also provided of profiling the donor capability of a cell or population of cells for cell therapy, such methods comprising evaluating the cell or the population of cells for predicted function. A predicted cell function may be evaluated by assaying one or more cell parameters. Further, cells and cell therapy products manufactured according to such methods are provided.

Provided herein are methods related to delivery of stem cell-derived cell therapies, including stem cell derived islet cell therapies, and related compositions, uses and articles of manufacture. In particular embodiments, the methods relate administering stem cell-derived islet cells. In some embodiments, the subject has a beta cell related disorder, such as diabetes (e.g. Type I diabetes).

Provided herein are lipid particles, including viral-based particles, comprising Paramyxovirus glycoproteins having reduced glycosylation, and in some aspects, comprise variant G/H proteins. Also provided are methods for producing and modifying lipid particles, including viral-based particles, wherein the particle has reduced glycosylation of the G/H protein, as well as methods for using the particles.

Provided herein are lipid particles and compositions thereof for delivery of heterologous proteins, including genome-modifying agents, to cells.

Disclosed herein are engineered cells and/or hypoimmunogenic cells including engineered cells and/or hypoimmunogenic stem cells, engineered cells and/or hypoimmunogenic cells differentiated therefrom, and/or engineered cells and/or hypoimmunogenic CAR-T cells (primary or differentiated from engineered and/or hypoimmunogenic stem cells) and related methods of their use and generation comprising regulatable reduced expression of one or more MHC class I and/or MHC class II human leukocyte antigen molecules and regulatable overexpression of CD47. Provided herein are cells further exhibiting reduced expression of T-cell receptors.

Provided herein are methods of dosing engineered islet cells that include functional modified beta cell containing one or more modifications, such as genetic modifications. In some embodiments, the engineered islets are hypoimmunogenic cells. In some embodiments, the one or more modifications reduce or eliminate expression of one or more MHC class I and/or MHC class II human leukocyte antigens and also increase expression of one or more tolerogenic factors, such as CD47. In some embodiments, the subject has a beta cell related disorder, such as diabetes (e.g. Type I diabetes).

Provided herein are methods of transducing or delivering an exogenous agent to a cell using a viral vector pseudotyped with a paramyxovirus and an inhibitor of the mammalian target of rapamycin (mTOR). In some embodiments, the methods can further include the administration of an antiviral restriction factor inhibitor and/or a cytokine.

The present disclosure provides engineered CD47 proteins and uses thereof. Also disclosed are poly nucleotides encoding the engineered CD47 protein, vectors comprising the polynucleotides, cells comprising the engineered proteins and/or the vectors, and compositions comprising the engineered CD47 protein.

Provided herein are methods of transducing resting or non-activated T cells using CD8-targeted viral vectors.

The present disclosure provides methods and compositions for administering to a subject in need thereof a CD47-SIRPα blockade agent, wherein the subject was previously administered a population of cells engineered to express an exogenous CD47 polypeptide.