Therapeutic Gene Editing Strategies Using CRISPR-Cas9 for the β-hemoglobinopathies

Overview

Journal J Biomed Res

Specialty General Medicine

Date 2020 Dec 22

PMID 33349624

Citations 5

Authors

James B Papizan

Shaina N Porter

Akshay Sharma

Shondra M Pruett-Miller

Affiliations

Soon will be listed here.

Abstract

With advancements in gene editing technologies, our ability to make precise and efficient modifications to the genome is increasing at a remarkable rate, paving the way for scientists and clinicians to uniquely treat a multitude of previously irremediable diseases. CRISPR-Cas9, short for clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9, is a gene editing platform with the ability to alter the nucleotide sequence of the genome in living cells. This technology is increasing the number and pace at which new gene editing treatments for genetic disorders are moving toward the clinic. The β-hemoglobinopathies are a group of monogenic diseases, which despite their high prevalence and chronic debilitating nature, continue to have few therapeutic options available. In this review, we will discuss our existing comprehension of the genetics and current state of treatment for β-hemoglobinopathies, consider potential genome editing therapeutic strategies, and provide an overview of the current state of clinical trials using CRISPR-Cas9 gene editing.

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References

Sankaran V, Xu J, Ragoczy T, Ippolito G, Walkley C, Maika S . Developmental and species-divergent globin switching are driven by BCL11A. Nature. 2009; 460(7259):1093-7. PMC: 3749913. DOI: 10.1038/nature08243. View

Orkin S, Kazazian Jr H, Antonarakis S, Ostrer H, Goff S, Sexton J . Abnormal RNA processing due to the exon mutation of beta E-globin gene. Nature. 1982; 300(5894):768-9. DOI: 10.1038/300768a0. View

Huang X, Wang Y, Yan W, Smith C, Ye Z, Wang J . Production of Gene-Corrected Adult Beta Globin Protein in Human Erythrocytes Differentiated from Patient iPSCs After Genome Editing of the Sickle Point Mutation. Stem Cells. 2015; 33(5):1470-9. PMC: 4628786. DOI: 10.1002/stem.1969. View

Yawn B, Buchanan G, Afenyi-Annan A, Ballas S, Hassell K, James A . Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014; 312(10):1033-48. DOI: 10.1001/jama.2014.10517. View

Gladwin M, Sachdev V, Jison M, Shizukuda Y, Plehn J, Minter K . Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med. 2004; 350(9):886-95. DOI: 10.1056/NEJMoa035477. View

Sather B, Romano Ibarra G, Sommer K, Curinga G, Hale M, Khan I . Efficient modification of CCR5 in primary human hematopoietic cells using a megaTAL nuclease and AAV donor template. Sci Transl Med. 2015; 7(307):307ra156. PMC: 4790757. DOI: 10.1126/scitranslmed.aac5530. View

Zeng J, Wu Y, Ren C, Bonanno J, Shen A, Shea D . Therapeutic base editing of human hematopoietic stem cells. Nat Med. 2020; 26(4):535-541. PMC: 7869435. DOI: 10.1038/s41591-020-0790-y. View

Sankaran V, Menne T, Xu J, Akie T, Lettre G, Van Handel B . Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A. Science. 2008; 322(5909):1839-42. DOI: 10.1126/science.1165409. View

Pattanayak V, Lin S, Guilinger J, Ma E, Doudna J, Liu D . High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity. Nat Biotechnol. 2013; 31(9):839-43. PMC: 3782611. DOI: 10.1038/nbt.2673. View

10.

Rochette J, Craig J, Thein S . Fetal hemoglobin levels in adults. Blood Rev. 1994; 8(4):213-24. DOI: 10.1016/0268-960x(94)90109-0. View

11.

Canela A, Sridharan S, Sciascia N, Tubbs A, Meltzer P, Sleckman B . DNA Breaks and End Resection Measured Genome-wide by End Sequencing. Mol Cell. 2016; 63(5):898-911. PMC: 6299834. DOI: 10.1016/j.molcel.2016.06.034. View

12.

Powars D, Chan L, Hiti A, Ramicone E, Johnson C . Outcome of sickle cell anemia: a 4-decade observational study of 1056 patients. Medicine (Baltimore). 2005; 84(6):363-376. DOI: 10.1097/01.md.0000189089.45003.52. View

13.

Weatherall D . Phenotype-genotype relationships in monogenic disease: lessons from the thalassaemias. Nat Rev Genet. 2001; 2(4):245-55. DOI: 10.1038/35066048. View

14.

Wienert B, Wyman S, Richardson C, Yeh C, Akcakaya P, Porritt M . Unbiased detection of CRISPR off-targets in vivo using DISCOVER-Seq. Science. 2019; 364(6437):286-289. PMC: 6589096. DOI: 10.1126/science.aav9023. View

15.

Crosetto N, Mitra A, Silva M, Bienko M, Dojer N, Wang Q . Nucleotide-resolution DNA double-strand break mapping by next-generation sequencing. Nat Methods. 2013; 10(4):361-5. PMC: 3651036. DOI: 10.1038/nmeth.2408. View

16.

Ye L, Wang J, Tan Y, Beyer A, Xie F, Muench M . Genome editing using CRISPR-Cas9 to create the HPFH genotype in HSPCs: An approach for treating sickle cell disease and β-thalassemia. Proc Natl Acad Sci U S A. 2016; 113(38):10661-5. PMC: 5035856. DOI: 10.1073/pnas.1612075113. View

17.

Haeussler M, Schonig K, Eckert H, Eschstruth A, Mianne J, Renaud J . Evaluation of off-target and on-target scoring algorithms and integration into the guide RNA selection tool CRISPOR. Genome Biol. 2016; 17(1):148. PMC: 4934014. DOI: 10.1186/s13059-016-1012-2. View

18.

Liu P, Keller J, Ortiz M, Tessarollo L, Rachel R, Nakamura T . Bcl11a is essential for normal lymphoid development. Nat Immunol. 2003; 4(6):525-32. DOI: 10.1038/ni925. View

19.

Xu J, Peng C, Sankaran V, Shao Z, Esrick E, Chong B . Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing. Science. 2011; 334(6058):993-6. PMC: 3746545. DOI: 10.1126/science.1211053. View

20.

Platt O, Orkin S, Dover G, Beardsley G, Miller B, Nathan D . Hydroxyurea enhances fetal hemoglobin production in sickle cell anemia. J Clin Invest. 1984; 74(2):652-6. PMC: 370519. DOI: 10.1172/JCI111464. View