Aerosol delivery of an enhanced helper-dependent adenovirus formulation to rabbit lung using an intratracheal catheter

Koehler, David R.; Frndova, Helena; Leung, Kitty; Louca, Emily; Palmer, D. Jason; Ng, Philip; McKerlie, Colin; Cox, P. Gerard; Coates, Allan L.; Hu, Jim

doi:10.1002/jgm.797

Cited by 64 publications

(58 citation statements)

References 61 publications

(71 reference statements)

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“…The decrease in viability observed with the Aeroprobe was not unexpected as only 40% of viable particles were recovered after aerosolization of helperdependent adenovirus vectors through catheters rated at 8 mm, rising to 80% with 15 mm, respectively. 17 (3) In addition, we were able to compare virus distribution after catheter-based segmental administration and Trudell AeroProbe aerosolization. Delivery by instillation results in patchy expression in the lungs likely due to the uneven distribution and pooling effect from the delivery of a bolus.…”

Section: Discussionmentioning

confidence: 99%

“…The predicted aerosol droplet size generated by this catheter is considerably larger (5-10 mm) than would normally be expected to result in deposition in the terminal bronchioles or alveolar regions. However, intratracheal aerosolization of similar size droplets to the rabbit lung, or of droplets with a mass median aerodynamic diameter of 430 mm in the mouse, has been shown to give deposition to airways of all sizes and even into the alveolar regions 17,18 suggesting that the droplet size is not so critical when generated intratracheally.…”

Section: Discussionmentioning

confidence: 99%

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Validation of recombinant Sendai virus in a non-natural host model

et al. 2010

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We have previously shown that recombinant Sendai virus (SeV) vector, derived from murine parainfluenza virus, is one of the most efficient vectors for airway gene transfer. We have also shown that SeV-mediated transfection on second administration, although reduced by 60% when compared with levels achieved after a single dose, is still high because of the efficient transfection achieved by SeV vector in murine airways. Here, we show that these levels further decrease on subsequent doses. In addition, we validated SeV vector repeat administration in a non-natural host model, the sheep. As part of these studies we first assessed viral stability in a Pari LC Plus nebuliser, a polyethylene catheter (PEC) and the Trudell AeroProbe. We also compared the distribution of gene expression after PEC and Trudell AeroProbe administration and quantified virus shedding after sheep transduction. In addition, we show that bronchial brushings and biopsies, collected in anaesthetized sheep, can be used to assess SeV-mediated gene expression over time. Similar to mice, gene expression in sheep was transient and had returned to baseline values by day 14. In conclusion, the SeV vector should be strongly considered for lung-related applications requiring a single administration of the vector even though it might not be suitable for diseases requiring repeat administration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Validation of recombinant Sendai virus in a non-natural host model

et al. 2010

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“…44 This method was used to aerosolize HDAd expressing LacZ formulated in L-a-lysophosphatidylcholine (LPC; to open tight junctions) into the lungs of rabbits and resulted in extensive transduction of the airway epithelium in the trachea and lung (Figure 3). 44 For example, 66% of the airway epithelial cells in the trachea were transduced. All rabbits, including those Figure 2 Pseudo-hydrodynamic injection of HDAd into nonhuman primates.…”

Section: Hdad Delivered With An Intracorporeal Nebulizing Catheter Rementioning

confidence: 99%

Progress and prospects: gene therapy for genetic diseases with helper-dependent adenoviral vectors

Brunetti‐Pierri

2008

Gene Ther

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Preclinical studies in small and large animal models using helper-dependent adenoviral vectors (HDAds) have generated promising results for the treatment of genetic diseases. However, clinical translation is complicated by the dosedependent, capsid-mediated acute toxic response following systemic vector injection. With the advancements in vectorology, a better understanding of vector-mediated toxicity, and improved delivery methods, HDAds may emerge as an important vector for gene therapy of genetic diseases and this report highlights recent progress and prospects in this field.

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“…This greatly enhances transduction of the cilated airway epithelium. 18,19 We considered that LPC, a phospholipid, might interact with the virion coat proteins and inhibit antibody binding to the virus. We tested this hypothesis using the ELISA system described above and immune mouse BALF.…”

Section: Repeat Airway Delivery Of Hd-ad Vectors Dr Koehler Et Almentioning

confidence: 99%