Development of formulations that enhance physical stability of viral vectors for gene therapy

Croyle, Maria A.; Cheng, Xuan; Wilson, James M.

doi:10.1038/sj.gt.3301527

Cited by 162 publications

(147 citation statements)

References 39 publications

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“…By this approach, vectors lost 50% activity within a day of storage at 4°C and eventually stabilized to 95% lost activity by 3 weeks. The loss of activity for this buffer contrasts with Croyle et al, in which only 10% activity was lost over 10 days at 4°C [35]. In this case, a more intricate lyophilization procedure was followed rather than our simple one, which may explain the difference in virus stability.…”

Section: Discussionmentioning

confidence: 59%

“…A simple lyophilization procedure was adapted from [35]. Ad vectors in KPBS and 1.0 M sucrose were flash frozen in capsules on dry ice to avoid dissolution of the water-soluble capsule and were lyophilized in a standard laboratory freeze-drying system.…”

Section: Discussionmentioning

confidence: 99%

“…A more recent study of lyophilized replication-competent Ad in tablets reported 33% loss in activity with the same buffer, but after extended 3-day lyophilization [44]. Alternatively, this difference in stability could be due to our flash-freezing of the virus directly into capsules versus the lyophilization in glass vials [35]. If so, one could hypothetically lyophilize in a vial and then transfer to a capsule.…”

Section: Discussionmentioning

confidence: 99%

“…A maximum of 20 μl per capsule of Ad vectors dissolved in potassium phosphate buffered saline (KPBS) with 1.0 M sucrose [35] were flash frozen in clear Quali-V ® HPMC capsules (Size 2, Qualicaps Inc., Whitsett, NC) on dry ice, placed in 1.5-ml microcentrifuge tubes, wrapped with weighing paper, and immediately placed in a pre-chilled LabConco 300-ml flask. The contents were freeze-dried using a FreezeZone® 4.5 L Benchtop Freeze Dry System 77500 (LabConco, Kansas City, MO) for 2 hr at −50ºC with an initial vacuum of 133 × 10 −3 mBar and a final vacuum of 3 × 10 −3 mBar.…”

Section: Lyophilization Of Adenoviral Vectorsmentioning

confidence: 99%

“…Ad vectors have previously been lyophilized in various buffers using a multi-stage single shelf lyophilizer showing losses of one to five logs of activity compared to pre-lyophilized Ad [35]. We chose the optimal buffer of KPBS with 1 M sucrose in the Croyle et al study for all Ad vectors requiring lyophilization.…”

Section: Adenoviral Vector Lyophilization and Stability Assaymentioning

confidence: 99%

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Oral immunization of rhesus macaques with adenoviral HIV vaccines using enteric-coated capsules

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Targeted delivery of vaccine candidates to the gastrointestinal (GI) tract holds potential for mucosal immunization, particularly against mucosal pathogens like the human immunodeficiency virus (HIV). Among the different strategies for achieving targeted release in the GI tract, namely the small intestine, pH sensitive enteric coating polymers have been shown to protect solid oral dosage forms from the harsh digestive environment of the stomach and dissolve relatively rapidly in the small intestine by taking advantage of the luminal pH gradient. We developed an enteric polymethacrylate formulation for coating hydroxy-propyl-methyl-cellulose (HPMC) capsules containing lyophilized Adenoviral type 5 (Ad5) vectors expressing HIV-1 gag and a string of six highly-conserved HIV-1 envelope peptides representing broadly cross-reactive CD4 + and CD8 + T cell epitopes. Oral immunization of rhesus macaques with these capsules primed antigen-specific mucosal and systemic immune responses and subsequent intranasal delivery of the envelope peptide cocktail using a mutant cholera toxin adjuvant boosted cellular immune responses including, antigen-specific intracellular IFN-γ-producing CD4 + and CD8 + effector memory T cells in the intestine. These results suggest that the combination of oral adenoviral vector priming followed by intranasal protein/peptide boosting may be an effective mucosal HIV vaccination strategy for targeting viral antigens to the GI tract and priming systemic and mucosal immunity.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Lyophilization Of Adenoviral Vectorsmentioning

confidence: 99%

Section: Adenoviral Vector Lyophilization and Stability Assaymentioning

confidence: 99%

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Adenovirus vectors in hematopoietic stem cell genome editing

Lieber

2019

FEBS Letters

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Genome editing of hematopoietic stem cells (HSCs) represents a therapeutic option for a number of hematological genetic diseases, as HSCs have the potential for self-renewal and differentiation into all blood cell lineages. This review presents advances of genome editing in HSCs utilizing adenovirus vectors as delivery vehicles. We focus on capsid-modified, helper-dependent adenovirus vectors that are devoid of all viral genes and therefore exhibit an improved safety profile. We discuss HSC genome engineering for several inherited disorders and infectious diseases including hemoglobinopathies, Fanconi anemia, hemophilia, and HIV-1 infection by ex vivo and in vivo editing in transgenic mice, nonhuman primates, as well as in human CD34 + cells. Mechanisms of therapeutic gene transfer including episomal expression of designer nucleases and base editors, transposase-mediated random integration, and targeted homology-directed repair triggered integration into selected genomic safe harbor loci are also reviewed.

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Development of formulations that enhance physical stability of viral vectors for gene therapy

Cited by 162 publications

References 39 publications

Oral immunization of rhesus macaques with adenoviral HIV vaccines using enteric-coated capsules

Oral immunization of rhesus macaques with adenoviral HIV vaccines using enteric-coated capsules

Drug Delivery Systems

Adenovirus vectors in hematopoietic stem cell genome editing

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