Differential cxcr4 expression on hematopoietic progenitor cells versus stem cells directs homing and long-term engraftment
AssigneeChildren's Hospital Medical Center
InventorPunam MALIK
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Abstract
Compositions and methods for delivering a protein of interest such as a cell homing molecule (e.g., CXCR4) into host cells (e.g., to hematopoietic cells). The compositions and methods provided herein may be used to enhance homing and long-term engraftment of hematopoietic cells post transplantation.
Claims54
A virus-like particle (VLP), comprising a protein shell that comprises (a) a protein of interest, which optionally is a cell homing molecule, and (b) one or more viral surface proteins;
- wherein when entering a host cell, the protein of interest detaches from the VLP and delivers to the host cell;
- optionally wherein the protein of interest is displayed on the surface of the host cell.
A fusion protein comprising a CXCR4 polypeptide fused to a viral protein R (Vpr) fragment, wherein the Vpr fragment is devoid of toxicity.
A population of hematopoietic cells comprising modified hematopoietic cells, which comprises an exogenous cell homing molecule and optionally a transgene of interest;
- wherein the modified hematopoietic cells have higher homing and engraftment activity relative to counterpart hematopoietic cells lacking the exogenous cell homing molecule post transplantation to a subject.
A gene therapy method, comprising:
- (i) isolating a population of hematopoietic cells from a first subject;
- (ii) introducing into the population of hematopoietic cells (a) a transgene encoding a therapeutic agent and (b) a cell homing molecule to produce a population of modified hematopoietic cells;
- and
- (iii) administering the modified hematopoietic cells to a second subject.
A method for improving engraftment of long-term repopulating cells (LTRCs) in a subject, the method comprising administering a population of hematopoietic cells comprising LTRCs to a subject in need thereof by intra-bone marrow (IBM) injection, wherein the LTRCs comprise CD34+ and CD38−cells, and wherein the population of hematopoietic cells comprise no more than 10-20%% CD34+and CD38+cells.
Dependencies are inferred from the claim text.