Post-natal transplantation of factor VIII-expressing cells for treatment of hemophilia
AssigneesWake Forest University Health Sciences, Emory University, Children's Healthcare of Atlanta, Inc.
InventorsMaria Graca N.D. Almeida-Porada, Christopher D. Porada, Anthony Atala, Christopher B. Doering, H. Trent Spencer
Life of this patent
Estimating the term…
Abstract
Disclosed herein are method of treating hemophilia A in a subject comprising injecting the subject with mesenchymal stromal/stem cells (MSC) modified to express high levels of Factor VIII protein. The MSC are isolated prenatally, at birth, or after the subject's birth. The modified MSC may also express high levels von Willebrand factor protein.
Claims19
A method of post-natally treating a subject diagnosed with hemophilia A, comprising:
- (a) providing isolated c-kit+ mesenchymal stem/stromal cells (MSC), wherein the MSC have been isolated for positive expression of c-kit;
- (b) modifying the isolated c-kit+ MSC of step (a) to express high levels of Factor VIII protein thereby generating modified MSC,
- wherein the modified MSC comprise at least one of modified amniotic fluid MSC, modified placental tissue MSC, or modified umbilical cord tissue MSC,
- wherein the isolated c-kit+ MSC are modified to comprise a codon-optimized Factor VIII gene sequence comprising one or more genetic modifications that increase Factor VIII protein expression, Factor VIII protein stability, or both, and wherein the Factor VIII protein comprises human Factor VIII A2 and C2 domains and porcine Factor VIII A1, A3, and C1 domains, and
- wherein the codon-optimized Factor VIII gene sequence comprises SEQ ID NO:12;
- (c) generating an expanded modified MSC population by in vitro culturing the modified MSC;
- and
- (d) injecting the expanded modified MSC population into the subject.
A method of post-natally treating a subject prenatally diagnosed as having hemophilia A, comprising:
- (a) providing isolated c-kit+ mesenchymal stem/stromal cells (MSC), wherein the MSC have been isolated for positive expression of c-kit, wherein the MSC are isolated from at least one of amniotic fluid, placental tissue, or umbilical cord tissue obtained at the subject's birth or prenatally from the subject's mother;
- (b) modifying the isolated c-kit+ MSC of step (a) to express high levels of Factor VIII protein thereby generating modified c-kit+ MSC,
- wherein the modified c-kit+ MSC comprise a codon-optimized Factor VIII gene sequence comprising one or more genetic modifications that increase Factor VIII protein expression, Factor VIII protein stability, or both, and
- wherein the Factor VIII protein comprises human Factor VIII A2 and C2 domains and porcine Factor VIII A1, A3, and C1 domains, and
- wherein the codon-optimized Factor VIII gene sequence comprises SEQ ID NO:12;
- (c) generating an expanded modified MSC population by in vitro culturing the modified MSC;
- and
- (d) injecting the expanded modified MSC population into the subject.
Dependencies are inferred from the claim text.