US 11,701,437 B2
Systemic delivery of polypeptides
Denitsa M. Milanova, Boston, MA (US); George M. Church, Brookline, MA (US); Noah Davidsohn, Brookline, MA (US); Carl Schoellhammer, Medford, MA (US); Robert S. Langer, Newton, MA (US); Anna I. Mandinova, Newton, MA (US); and Carlo Giovanni Traverso, Newton, MA (US)
Assigned to President and Fellows of Harvard College, Cambridge, MA (US); Massachusetts Institute of Technology, Cambridge, MA (US); The Brigham and Women's Hospital, Inc., Boston, MA (US); and The General Hospital Corporation, Boston, MA (US)
Appl. No. 16/612,648
Filed by President and Fellows of Harvard College, Cambridge, MA (US); Massachusetts Institute of Technology, Cambridge, MA (US); The Brigham and Women's Hospital, Inc., Boston, MA (US); and The General Hospital Corporation, Boston, MA (US)
PCT Filed May 14, 2018, PCT No. PCT/US2018/032600
§ 371(c)(1), (2) Date Nov. 11, 2019,
PCT Pub. No. WO2018/209359, PCT Pub. Date Nov. 15, 2018.
Claims priority of provisional application 62/505,308, filed on May 12, 2017.
Prior Publication US 2020/0197538 A1, Jun. 25, 2020
Int. Cl. A61K 48/00 (2006.01); A61K 47/69 (2017.01); A61N 7/00 (2006.01); C12N 15/86 (2006.01); A61K 9/70 (2006.01)
CPC A61K 48/0075 (2013.01) [A61K 47/6901 (2017.08); A61N 7/00 (2013.01); C12N 15/86 (2013.01); A61K 9/7023 (2013.01); C12N 2750/14143 (2013.01); C12N 2750/14145 (2013.01); C12N 2750/14151 (2013.01); C12N 2810/859 (2013.01)] 34 Claims
 
1. A method of systemic delivery of a polypeptide to a subject comprising genetically modifying target skin cells within skin of a subject comprising
administering to the subject an engineered virus comprising one or more foreign nucleic acid sequences encoding one or more target polypeptides, wherein the engineered virus is an adeno-associated viral vector,
wherein the one or more foreign nucleic acid sequences of the engineered virus are introduced into the target skin cells within the skin to produce genetically modified skin cells, and wherein the genetically modified skin cells produce the one or more target polypeptides by expression of the one or more foreign nucleic acid sequences, and
wherein the one or more target polypeptides are excreted from the genetically modified skin cells and are introduced systemically within the subject.