SRT at ASGCT | Abstract 465

INTRODUCTION
Lentiviral vectors (LVV) encoding for erythroid-specific expression of a T87Q variant of adult human β-globin (βT87Q) have been used in multiple clinical trials. Despite the FDA approval of β-globin gene therapies, Lyfgenia and Zynteglo, a reliable companion diagnostic for the vector-encoded gene product is lacking. Protein-based assays (immunocytochemistry, flow cytometry) are unable to distinguish the single βT87Q amino acid change. Reversed phase high performance liquid chromatography (RP-HPLC) is not quantitative due to the absence of a βT87Q reference standard, and remains a technically demanding method. With these limitations in mind, our group developed a T87Q variant-specific nucleotide amplification assay to selectively and quantitatively detect the βT87Q globin transcript, even in the presence of wild-type (WT) β-globin.

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