Pseudotyped human lentiviral vector-mediated gene transfer to airway epithelia in vivo

Characterization of novel safe lentiviral vectors derived from simian immunodeficiency virus (SIVmac251) that efficiently transduce mature human dendritic cells

“…25,[35][36][37][38][39] To be of real benefit for in vivo administration protocols, such vectors should be infectious at low MOIs, since only MOIs of far less than one would be applicable in vivo. Here, we have shown that SIV-based vectors could efficiently transduce nonproliferating monocyte-derived mature human DCs, at an MOI of one infectious particle per target cell, thus establishing the value of these novel lentiviral vectors.…”

“…31,32 The development of lentivirus-based vectors, particularly those derived from HIV-1, is a rapidly progressing field and several studies have demonstrated that these vectors can transduce nondividing cells ex vivo 15,26,33,34 and in vivo. 25,[35][36][37][38][39] Despite all the safeguards that have progressively been introduced in lentiviral vectors, the clinical acceptance of vectors derived from pathogenic lentiviruses is still a subject of debate. It is therefore essential to design vectors derived from a wide range of lentivirus types and to examine comparatively their properties in terms of transduction efficiency and biosafety.…”

Directed evolution of adeno-associated virus to an infectious respiratory virus

“…To achieve evolutionary success, viruses may alter or compromise each of these steps to reduce the efficiency of infection and achieve a balance between the production of viruses that spread, but do not cause, host (and hence virus) extinction. This concept is strikingly illustrated by the inefficiency, and consequent lack of therapeutic end points, of gene transfer vectors based on respiratory viruses for respiratory diseases (3)(4)(5)(6). A better understanding of evolutionary principles governing natural viral evolution will drive more advanced methods to successfully engineer novel virus-based gene therapeutics.…”

Lentivirus-mediated gene transfer to the respiratory epithelium: a promising approach to gene therapy of cystic fibrosis

“…65 Finally, the picture is further complicated by the localization of stem cells for surface airway epithelium to upper tracheal gland ducts and to distinct foci in the glandless distal trachea. 66 Overall, the studies previously mentioned 39,41,42,44 indicate that both HIV-1-and FIV-derived vectors mediate long-term gene expression by targeting a 'progenitor cell' compartment. A recent report strongly suggests such a possibility.…”

“…An HIV-1-derived vector transduced polarized tracheal epithelial cells from the apical surface only in the presence of the calcium chelator ethyleneglycol-tetraacetic acid (EGTA) and, however, at a much lower overall efficiency than was observed for polarized alveolar epithelial cells. 40 Johnson et al 41 showed that direct in vivo delivery of VSV-G-pseudotyped HIV-1-derived vector to the nasal Lentivirus-mediated gene transfer in CF E Copreni et al epithelium of mice and rats failed to mediate gene transfer unless inhalation exposure to sulfur dioxide (SO 2 ) was applied. Vector was instilled 1-2 h after SO 2 administration.…”