Matches in SemOpenAlex for { <https://semopenalex.org/work/W2563764103> ?p ?o ?g. }
Showing items 1 to 90 of
90
with 100 items per page.
- W2563764103 abstract "Compared to other integrating viral vectors, foamy virus (FV) vectors have several distinct advantages as a gene transfer tool, including: the ability to carry larger expression cassettes, the increased stability due to a DNA genome formed in developing vector particles, and the random integration pattern without preference for promoter regions or active genes as is the case with gamma-retroviral and lentiviral vectors. In addition, the FV envelope has tropism for most cell types and is not associated with disease in humans. Combined, these properties make FV vectors the ideal candidate for gene therapy application. Proof of principle was provided by Bauer et al. (Nat. Med. 2008) showing cure of canine Leukocyte Adhesion Deficiency (LAD) using autologous CD34+ cells transduced with FV vector carrying the CD18 gene, without short or long-term adverse effects. Here we demonstrate the optimization of large scale manufacturing of FV vector carrying the human CD18 gene for the treatment of human LAD. As compared to the methods used in the canine LAD study, a 60-fold increase in FV-CD18 titer was observed using a combination of polyethylenimine (PEI) transfection and use of a codon-optimized gag, from approximately 1.70E+04 to 1.00E+06 Infectious Units/mL (IU/mL) on Raw 264.7 cells. An evaluation of purification strategies showed efficient vector purification and concentration of FV vector through a combination of heparin-affinity chromatography on the AKTA ready, a disposable fluid path chromatography unit, tangential flow filtration and ultracentrifugation, with an overall 5000-fold concentration and 20-30% recovery. This approach was compatible with large scale manufacturing in compliance with Good Manufacturing Practices (GMP). Although 5% DMSO is needed for optimal recovery of infectious FV vector from -80°C storage, highly concentrated vector can be diluted to reduce the DMSO concentration and toxicity to CD34+ cells, while maintaining effective transduction rates of up to 50%. This process is currently being finalized for clinical manufacturing in support of a Phase I trial for the treatment of LAD.Note: MN and DL equally contributed to this study." @default.
- W2563764103 created "2017-01-06" @default.
- W2563764103 creator A5011539486 @default.
- W2563764103 creator A5020792222 @default.
- W2563764103 creator A5021982985 @default.
- W2563764103 creator A5023950205 @default.
- W2563764103 creator A5058890610 @default.
- W2563764103 creator A5059743365 @default.
- W2563764103 creator A5066584377 @default.
- W2563764103 creator A5067822812 @default.
- W2563764103 creator A5073161179 @default.
- W2563764103 creator A5075340416 @default.
- W2563764103 creator A5083240314 @default.
- W2563764103 date "2015-05-01" @default.
- W2563764103 modified "2023-09-24" @default.
- W2563764103 title "461. Scale-Up and Manufacturing of High-Titer Foamy Virus Vector Containing Human CD18 for the Treatment of Leukocyte Adhesion Deficiency" @default.
- W2563764103 doi "https://doi.org/10.1016/s1525-0016(16)34070-9" @default.
- W2563764103 hasPublicationYear "2015" @default.
- W2563764103 type Work @default.
- W2563764103 sameAs 2563764103 @default.
- W2563764103 citedByCount "1" @default.
- W2563764103 countsByYear W25637641032015 @default.
- W2563764103 crossrefType "journal-article" @default.
- W2563764103 hasAuthorship W2563764103A5011539486 @default.
- W2563764103 hasAuthorship W2563764103A5020792222 @default.
- W2563764103 hasAuthorship W2563764103A5021982985 @default.
- W2563764103 hasAuthorship W2563764103A5023950205 @default.
- W2563764103 hasAuthorship W2563764103A5058890610 @default.
- W2563764103 hasAuthorship W2563764103A5059743365 @default.
- W2563764103 hasAuthorship W2563764103A5066584377 @default.
- W2563764103 hasAuthorship W2563764103A5067822812 @default.
- W2563764103 hasAuthorship W2563764103A5073161179 @default.
- W2563764103 hasAuthorship W2563764103A5075340416 @default.
- W2563764103 hasAuthorship W2563764103A5083240314 @default.
- W2563764103 hasBestOaLocation W25637641031 @default.
- W2563764103 hasConcept C104317684 @default.
- W2563764103 hasConcept C111599444 @default.
- W2563764103 hasConcept C153911025 @default.
- W2563764103 hasConcept C159047783 @default.
- W2563764103 hasConcept C171779818 @default.
- W2563764103 hasConcept C2776342803 @default.
- W2563764103 hasConcept C32470452 @default.
- W2563764103 hasConcept C40767141 @default.
- W2563764103 hasConcept C53122370 @default.
- W2563764103 hasConcept C54009773 @default.
- W2563764103 hasConcept C553184892 @default.
- W2563764103 hasConcept C55493867 @default.
- W2563764103 hasConcept C86803240 @default.
- W2563764103 hasConcept C92087593 @default.
- W2563764103 hasConceptScore W2563764103C104317684 @default.
- W2563764103 hasConceptScore W2563764103C111599444 @default.
- W2563764103 hasConceptScore W2563764103C153911025 @default.
- W2563764103 hasConceptScore W2563764103C159047783 @default.
- W2563764103 hasConceptScore W2563764103C171779818 @default.
- W2563764103 hasConceptScore W2563764103C2776342803 @default.
- W2563764103 hasConceptScore W2563764103C32470452 @default.
- W2563764103 hasConceptScore W2563764103C40767141 @default.
- W2563764103 hasConceptScore W2563764103C53122370 @default.
- W2563764103 hasConceptScore W2563764103C54009773 @default.
- W2563764103 hasConceptScore W2563764103C553184892 @default.
- W2563764103 hasConceptScore W2563764103C55493867 @default.
- W2563764103 hasConceptScore W2563764103C86803240 @default.
- W2563764103 hasConceptScore W2563764103C92087593 @default.
- W2563764103 hasLocation W25637641031 @default.
- W2563764103 hasOpenAccess W2563764103 @default.
- W2563764103 hasPrimaryLocation W25637641031 @default.
- W2563764103 hasRelatedWork W153566633 @default.
- W2563764103 hasRelatedWork W1598659427 @default.
- W2563764103 hasRelatedWork W1981153909 @default.
- W2563764103 hasRelatedWork W2037994089 @default.
- W2563764103 hasRelatedWork W2085645098 @default.
- W2563764103 hasRelatedWork W2091929928 @default.
- W2563764103 hasRelatedWork W2327888552 @default.
- W2563764103 hasRelatedWork W2417264068 @default.
- W2563764103 hasRelatedWork W2423471975 @default.
- W2563764103 hasRelatedWork W2532266752 @default.
- W2563764103 hasRelatedWork W2562161236 @default.
- W2563764103 hasRelatedWork W2562314363 @default.
- W2563764103 hasRelatedWork W2567673922 @default.
- W2563764103 hasRelatedWork W2570649395 @default.
- W2563764103 hasRelatedWork W2783222048 @default.
- W2563764103 hasRelatedWork W2991496875 @default.
- W2563764103 hasRelatedWork W3042201775 @default.
- W2563764103 hasRelatedWork W3147629905 @default.
- W2563764103 hasRelatedWork W3198101696 @default.
- W2563764103 hasRelatedWork W2187054508 @default.
- W2563764103 isParatext "false" @default.
- W2563764103 isRetracted "false" @default.
- W2563764103 magId "2563764103" @default.
- W2563764103 workType "article" @default.