Abstract
BackgroundThe treatment of many cancers and genetic diseases relies on novel engraftment approaches such as cell therapy and hematopoietic stem cell transplantation (HSCT). However, these methods are hindered by the alloreactive immune responses triggered by incompatible human leukocyte antigen (HLA) molecules. A successful HSCT procedure requires the eradication of donor and recipient HLA alloimmunization. Eliminating HLA-A gene expression using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 nuclease (CRISPR/Cas9) could be a great approach to increase the possibility of a successful HSCT through extending pool of unrelated donors.ResultsOur dual gRNA approach introduced a large deletion in the HLA-A gene. Among 22 single-cloned cells, two clones (9.09%) and 11 clones (50%) received homozygous and heterozygous large deletions, respectively. Finally, the real-time PCR results also revealed that HLA-A gene expression was diminished significantly.ConclusionThe results suggested that CRISPR/Cas9 could be used as an efficient technique to introduce HLA-A gene knockout; thus, it can considerably lessen the burden of finding a fully matched donor by lowering the alleles required for a successful HSCT.
Highlights
The treatment of many cancers and genetic diseases relies on novel engraftment approaches such as cell therapy and hematopoietic stem cell transplantation (HSCT)
The coding sequences which were elicited from IPD-IMGT/human leukocyte antigen (HLA) [15] were aligned simultaneously, and the appropriated guide Ribonucleic acid (RNA) (gRNA) were picked out among the consensus regions
AgRNA1 could target most of the HLA-A alleles, except
Summary
The treatment of many cancers and genetic diseases relies on novel engraftment approaches such as cell therapy and hematopoietic stem cell transplantation (HSCT). These methods are hindered by the alloreactive immune responses triggered by incompatible human leukocyte antigen (HLA) molecules. Serious challenges including stringent matching, donor insufficiency, engraftment rejection, and graft-versus-host disease (GVHD) may hinder the widespread clinical applications of this approach [1]. In this context, the major underlying issue is the incompatibility of HLA molecule expressed on the surface of various cells. These studies suggest that even the partial ablation of HLA expression can reduce the transplantation prerequisites and increase the chance
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