CRISPR/Cas9-mediated conversion of human platelet alloantigen allotypes

Zhang, Nanyan; Zhi, Huiying; Curtis, Brian R.; Rao, Sridhar; Jobaliya, Chintan; Poncz, Mortimer; French, Deborah L.; Newman, Peter J.

doi:10.1182/blood-2015-10-675751

Cited by 46 publications

(28 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…CRISPR‐based genome editing of an immortalized human erythroblast cell line (with subsequent erythroid differentiation) has allowed removal of five distinct antigens that would alleviate alloimmunization side effects in a subset of patients with rare RBC antigen profiles . Similarly, customized platelets with rare alloantigenic epitopes (HPA‐1b) have been generated by editing induced pluripotent stem cells and megakaryocyte‐like cells, offering future diagnostic and therapeutic applications for thrombocytopenia . Further, studies suggest that engineering induced pluripotent stem cells into reagent red cells with rare antigen phenotypes show promise for alleviating a great shortage of diagnostic cells for patients with complex alloantibody profiles .…”

Section: Future Therapeutic Applicationsmentioning

confidence: 99%

Clinical applications of CRISPR‐based genome editing and diagnostics

2019

View full text Add to dashboard Cite

Clustered regularly interspaced short palindromic repeats (CRISPR)‐driven genome editing has rapidly transformed preclinical biomedical research by eliminating the underlying genetic basis of many diseases in model systems and facilitating the study of disease etiology. Translation to the clinic is under way, with announced or impending clinical trials utilizing ex vivo strategies for anticancer immunotherapy or correction of hemoglobinopathies. These exciting applications represent just a fraction of what is theoretically possible for this emerging technology, but many technical hurdles must be overcome before CRISPR‐based genome editing technology can reach its full potential. One exciting recent development is the use of CRISPR systems for diagnostic detection of genetic sequences associated with pathogens or cancer. We review the biologic origins and functional mechanism of CRISPR systems and highlight several current and future clinical applications of genome editing.

show abstract

Section: Future Therapeutic Applicationsmentioning

confidence: 99%

Clinical applications of CRISPR‐based genome editing and diagnostics

2019

View full text Add to dashboard Cite

show abstract

“…To circumvent an immunological reaction against in vitro generated MK or PLTs, alternatively a genetic knock out [14,15] or knockdown [16] of HLA class I in the source cells is possible, targeting the conserved domain beta2-microglobulin by TALEN, CRISPR/Cas9 or RNA interference, respectively. As the complete absence of HLA class I is activating the recognition by natural killer (NK) cells, an HLA knock out is useful for the production of PLTs only, since PLTs are not recognized by NK cells [17], in contrast to MKs.…”

Section: Megakaryocytesmentioning

confidence: 99%

Large-Scale Cultures and Bioreactors for the Production of Megakaryocytes and Platelets

Baigger¹,

Eicke²,

Blasczyk³

et al. 2017

Adv Tech Biol Med

View full text Add to dashboard Cite

A constant rising demand on platelets has been observed which is associated with population ageing and rapid progresses in the development of advanced therapeutic strategies. Therefore, innovative attempts towards the in vitro production of platelets and their precursors are inevitable. Extensive research has been performed on the exploration of reliable cell sources and the establishment of efficient protocols for the differentiation of functional platelets. In particular, the design of bioreactors mimicking the bone marrow microenvironment has gained plenty of attention to achieve clinically relevant platelet yields. In this review, we summarize major advances and perspectives on the manufacture and application of in vitro generated megakaryocytes and platelets.

show abstract

“…iPSC-derived HLA class I-silenced MKs and PLTs have shown to escape antibody-mediated cytotoxicity in vitro and in vivo [63]. Also, CRISPR/Cas9 gene editing of PLT antigens in iPSCs was performed [64]. These approaches aim to reduce the immunogenicity of PLT transfusions towards the generation of universal PLT products.…”

Section: Pluripotent Stem Cellsmentioning

confidence: 99%

Towards the Manufacture of Megakaryocytes and Platelets for Clinical Application

Baigger¹,

Blasczyk²,

Figueiredo³

2017

Transfus Med Hemother

View full text Add to dashboard Cite

Platelet transfusions are used in standard clinical practice to prevent hemorrhage in patients suffering from thrombocytopenia or platelet dysfunctions. Recently, a constant rise on the demand of platelets for transfusion has been registered. This may be associated with several factors including demographic changes, population aging as well as incidence and prevalence of hematological diseases. In addition, platelet-regenerative properties have been started to be exploited in different areas such as tissue remodeling and anti-cancer therapies. These new applications are also expected to increase the future demand on platelets. Thus, in vitro generated platelets may constitute a highly desirable alternative to meet the rising demand on platelets. Several factors have been considered in the road trip of producing in vitro megakaryocytes and platelets for clinical application. From selection of the cell source, differentiation protocols and culture conditions to the design of optimal bioreactors, several strategies have been proposed to maximize production yields while preserving functionality. This review summarizes new advances in megakaryocyte and platelet differentiation and their production upscaling.

show abstract

CRISPR/Cas9-mediated conversion of human platelet alloantigen allotypes

Abstract: Key Points The genome of iPSCs has been edited to encode antigenically-distinct human platelet alloantigens. The iPSC-derived megakaryocyte progenitor cells express the designed alloantigens for diagnostic, investigative, and future therapeutic use.

Cited by 46 publications

References 49 publications

Clinical applications of CRISPR‐based genome editing and diagnostics

Clinical applications of CRISPR‐based genome editing and diagnostics

Large-Scale Cultures and Bioreactors for the Production of Megakaryocytes and Platelets

Towards the Manufacture of Megakaryocytes and Platelets for Clinical Application

Contact Info

Product

Resources

About