The potential of gene therapy approaches for the treatment of hemoglobinopathies: achievements and challenges.
Hemoglobinopathies, including β-thalassemia and sickle cell disease (SCD), are a heterogeneous group of commonly inherited disorders affecting the function or levels of hemoglobin. Disease phenotype can be severe with substantial morbidity and mortality. Bone marrow transplantation is curative, but limited to those patients with an appropriately matched donor. Genetic therapy, which utilizes a patient's own cells, is thus an attractive therapeutic option. Numerous therapies are currently in clinical trials or in development, including therapies utilizing gene replacement therapy using lentiviruses and the latest gene editing techniques. In addition, methods are being developed that may be able to expand gene therapies to those with poor access to medical care, potentially significantly decreasing the global burden of disease.
Division of Experimental Hematology and Cancer Biology,Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Michael A
MA
Goodman
Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
Punam
P
Malik
gene editing; gene therapy; hemoglobin; hemoglobinopathy; sickle cell anemia; thalassemia
Mol Ther. 2006 Jun;13(6):1110-20
16651028
Genome Res. 2014 Sep;24(9):1526-33
25096406
JAMA. 2014 Jul 2;312(1):48-56
25058217
Blood Cells Mol Dis. 2006 Jul-Aug;37(1):1-7
16814578
Biotechnol Bioeng. 2014 May;111(5):1048-53
23928856
Nature. 2010 Sep 16;467(7313):318-22
20844535
Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3107-10
1557419
Blood. 2011 Oct 27;118(17):4599-608
21881051
Sci Rep. 2015 Jul 09;5:12065
26156589
Hum Mol Genet. 2007 Nov 1;16(21):2616-25
17716993
Proc Natl Acad Sci U S A. 1986 May;83(10):3194-8
3458176
Ann N Y Acad Sci. 2010 Aug;1202:52-8
20712772
Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6728-32
7624311
Haematologica. 2008 Aug;93(8):1238-42
18556409
Science. 2009 Dec 11;326(5959):1501
19933106
Hum Gene Ther. 2011 Sep;22(9):1043-51
21867398
Haematologica. 2014 Jan;99(1):76-84
23872310
Nature. 2015 Apr 9;520(7546):186-91
25830891
Mol Ther. 2015 Sep;23(9):1465-74
26080908
J Blood Med. 2015 Feb 19;6:69-85
25737641
Stem Cells. 2015 May;33(5):1470-9
25702619
PLoS One. 2013 Nov 18;8(11):e80403
24260386
Blood. 2009 May 14;113(20):4856-65
19258595
Stem Cell Rev. 2015 Dec;11(6):900-8
26341105
Prog Clin Biol Res. 1989;316B:219-33
2694174
Hematol Oncol Clin North Am. 2014 Apr;28(2):199-216
24589262
Nature. 2012 Nov 1;491(7422):114-8
23000899
Blood. 2015 Apr 23;125(17):2597-604
25733580
Nature. 2015 Nov 12;527(7577):192-7
26375006
Nat Biotechnol. 2011 Feb;29(2):143-8
21179091
Blood. 1996 Mar 15;87(6):2518-24
8630419
Curr Gene Ther. 2014;14(6):461-72
25245091
Stem Cells. 2011 Nov;29(11):1717-26
21898685
Int J Hematol. 2011 Mar;93(3):301-10
21369857
JAMA. 2014 Sep 10;312(10):1033-48
25203083
Blood. 2010 Dec 9;116(24):5419-22
20813896
Mol Ther. 2003 Jul;8(1):108-17
12842434
Gene Ther. 2005 Nov;12(21):1591-600
15944728
Cell. 2006 Aug 25;126(4):663-76
16904174
Anemia. 2012;2012:507894
22778925
Science. 2009 Sep 18;325(5947):1512
19762636
J Virol. 1998 Oct;72(10):8150-7
9733856
Blood Cells Mol Dis. 1997;23(1):69-87
9215752
Proc Natl Acad Sci U S A. 1986 May;83(10):3496-9
3458192
EMBO J. 1994 Jul 1;13(13):3065-76
8039501
Nature. 2016 Jan 28;529(7587):490-5
26735016
Science. 1996 Apr 12;272(5259):263-7
8602510
J Virol. 1998 Dec;72(12):9873-80
9811723
Science. 2001 Dec 14;294(5550):2368-71
11743206
Mol Cell Biol. 1989 Apr;9(4):1426-34
2657395
Blood. 2007 Oct 1;110(7):2749-56
17606762
Cold Spring Harb Perspect Med. 2012 May;2(5):a011825
22553502
Nature. 2011 Jun 26;475(7355):217-21
21706032
Nature. 1988 Jan 7;331(6151):35-41
2893284
Blood. 2014 Jun 5;123(23):3578-84
24642749
J Clin Invest. 2013 Jul 1;:null
23863630
Blood. 2012 Oct 11;120(15):2945-53
22904296
Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13294-9
11069298
Science. 2009 Dec 11;326(5959):1509-12
19933107
Biotechniques. 1995 Nov;19(5):816-23
8588922
Transl Res. 2013 Apr;161(4):293-306
23337292
J Biol Chem. 2013 Nov 29;288(48):34671-9
24155235
Hum Mol Genet. 2009 Oct 15;18(R2):R216-23
19808799
Blood. 2003 Nov 1;102(9):3412-9
12855570
Stem Cells Dev. 2015 May 1;24(9):1053-65
25517294
Ann N Y Acad Sci. 2005;1054:308-16
16339679
Science. 2016 Jan 1;351(6268):84-8
26628643
Exp Hematol. 2015 May;43(5):346-51
25681747
J Clin Invest. 1970 Apr;49(4):635-42
5443168
Blood. 2011 Jul 7;118(1):19-27
21490337
Nature. 2000 Jul 6;406(6791):82-6
10894546
Cell. 2015 Oct 22;163(3):759-71
26422227
Blood Cells Mol Dis. 2000 Dec;26(6):613-9
11358353
Nucleic Acids Res. 2014 Jan;42(2):1365-78
24157834
Stem Cells Dev. 2006 Apr;15(2):278-85
16646674
Hum Mol Genet. 2011 Apr 15;20(R1):R14-20
21459777
Blood. 1993 Mar 1;81(5):1384-92
8443396
Cell. 1990 Nov 16;63(4):665-72
2225071
Am J Prev Med. 2011 Dec;41(6 Suppl 4):S398-405
22099364
Blood. 2003 Dec 15;102(13):4312-9
12933581