Compounds for improved viral transduction
Assigneebluebird bio, Inc.
InventorsGarrett Collins Heffner, Abraham Isaac Bassan
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Abstract
The present invention provides methods and compositions for improving the efficacy of viral transduction of cells. More particularly, the present invention provides methods and materials useful for safely and reliably improving the efficiency of methods for transducing cells, such as human hematopoietic stem cells (HSC), with viruses and/or viral vectors. The compositions and methods are useful for therapeutic indications amenable to treatment with hematopoietic stem cell gene therapies.
Claims56
A method for increasing the transduction efficiency of CD34+ hematopoietic stem and/or progenitor cells cultured with a lentivirus comprising:
- culturing the CD34+ hematopoietic stem and/or progenitor cells and the lentivirus in a culture medium that comprises a compound that increases prostaglandin EP receptor signaling, wherein the CD34+ hematopoietic stem and/or progenitor cells are cultured with the lentivirus during, or prior to, culture with the compound that increases prostaglandin EP receptor signaling, and wherein the transduction efficiency of CD34+ hematopoietic stem and/or progenitor cells cultured with the lentivirus is increased compared to the transduction efficiency of the CD34+ hematopoietic stem and/or progenitor cells cultured with the lentivirus in the absence of the compound that increases prostaglandin EP receptor signaling,
- wherein the compound that increases prostaglandin EP receptor signaling is selected from the group consisting of:
- prostaglandin E2 (PGE2), 16,16-dimethyl PGE2 and analogues thereof.
A method for increasing the transduction efficiency of CD34+ hematopoietic stem and/or progenitor cells cultured with a lentivirus comprising:
- culturing the CD34+ hematopoietic stern and/or progenitor cells and the lentivirus in a culture medium that comprises PGE2, wherein the CD34+ hematopoietic stem and/or progenitor cells are cultured with the lentivirus during, or prior to, culture with the PGE2, and wherein the transduction efficiency of CD34+ hematopoietic stem and/or progenitor cells cultured with the lentivirus is increased compared to the transduction efficiency of the CD34+ hematopoietic stem and/or progenitor cells cultured with the lentivirus in the absence of the PGE2.
A method for increasing the transduction efficiency of CD34+ hematopoietic stem and/or progenitor cells cultured with a lentivirus comprising:
- culturing the CD34+ hematopoietic stem and/or progenitor cells and the lentivirus in a culture medium that comprises 16,16-dimethyl PGE2, wherein the CD34+ hematopoietic stem and/or progenitor cells are cultured with the lentivirus during, or prior to, culture with the 16,16-dimethyl PGE2, and wherein the transduction efficiency of CD34+ hematopoietic stem and/or progenitor cells cultured with the lentivirus is increased compared to the transduction efficiency of the CD34+ hematopoietic stem and/or progenitor cells cultured with the lentivirus in the absence of the 16,16-dimethyl PGE2.
Dependencies are inferred from the claim text.