Figure 3.

Lenti-D LV encoding ALD protein used in the Bluebird Starbeam ALD-102 study. Lenti-D LVV is a replication defective, SIN, third-generation HIV-1 based LVV pseudotyped with glycoprotein (G) of the vesicular stomatitis virus (VSV-G), carrying human ABCD1 cDNA-derived sequences that encode the normal human ALDP. The vector sequences encoding the normal ALDP are under control of the MND promoter, which has been shown to drive expression of the transgene in HSCs. The vector is similar to that used in Cartier et al (CG1711 hALD) (59) in regard to the promotor used and ALDP cDNA but differs in elements of the vector backbone, including removal of the WPRE. Abbreviations: cPPT/FLAP, central polypurine tract; ΔU3, promoter/enhancer-deleted unique 3’; MND, myeloproliferative sarcoma virus enhancer with negative control region deleted, dl587rev primer-binding site substituted; ppt, 3’ poly purine tract; Ψ+, packaging signal; R, repeat; RRE, rev response element; U5, unique 5’ site. (Reproduced with permission from Eichler F, Duncan C, Musolino PL, et al. Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy. N Engl J Med. 2017;377 (17):1630–8.).