• Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency

      De Ravin, Suk S.; Wu, Xiaolin; Moir, Susan; Anaya-O'Brien, Sandra; Kwatemaa, Nana; Littel, Patricia; Theobald, Narda; Choi, Uimook; Su, Ling; Marquesen, Martha; et al. (American Association for the Advancement of Science, 2016-04-20)
      X-linked severe combined immunodeficiency (SCID-X1) is a profound deficiency of T, B, and natural killer (NK) cell immunity caused by mutations inIL2RGencoding the common chain (gammac) of several interleukin receptors. Gamma-retroviral (gammaRV) gene therapy of SCID-X1 infants without conditioning restores T cell immunity without B or NK cell correction, but similar treatment fails in older SCID-X1 children. We used a lentiviral gene therapy approach to treat five SCID-X1 patients with persistent immune dysfunction despite haploidentical hematopoietic stem cell (HSC) transplant in infancy. Follow-up data from two older patients demonstrate that lentiviral vector gammac transduced autologous HSC gene therapy after nonmyeloablative busulfan conditioning achieves selective expansion of gene-marked T, NK, and B cells, which is associated with sustained restoration of humoral responses to immunization and clinical improvement at 2 to 3 years after treatment. Similar gene marking levels have been achieved in three younger patients, albeit with only 6 to 9 months of follow-up. Lentiviral gene therapy with reduced-intensity conditioning appears safe and can restore humoral immune function to posthaploidentical transplant older patients with SCID-X1.
    • Stereoselective uptake of cell-penetrating peptides is conserved in antisense oligonucleotide polyplexes

      Favretto, Marco E.; Brock, Roland; Radboud University Medical Center (Wiley-VCH Verlag, 2014-11-10)
      Stereochemistry matters. A significant conceptual advancement is presented toward the understanding of how functional characteristics of delivery peptides can translate into functional characteristics of peptide-based oligoplexes