Perfluorochemical Liquid-Enhanced Adenoviral Vector Distribution and Expression in Lungs of Spontaneously Breathing Rodents

Weiss, Douglas J.; Tp, Strandjord; Jc, Jackson; Jg, Clark; Liggitt, Denny

doi:10.1080/019021499270222

Cited by 33 publications

(2 citation statements)

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“…PFC liquid has characteristics that are suited to use in the lungs. It is highly soluble in O 2 and CO 2 , and has a high density and low surface tension, allowing it to distribute throughout the conducting airways and alveoli [ 84 , 85 ]. Due to these properties, PFC liquid is proposed to act as a carrier to enable more efficient distribution of vector particles throughout the airways.…”

Section: Airway Surface Preparation Techniquesmentioning

confidence: 99%

“…Use of PFC liquid prior to vector administration improved AdV and AAV vector mediated gene transfer to the airways of rodents [ 84 , 86 , 88 ] and non-human primates [ 89 ]. Inhalation of nebulised PFC vapour has also been explored as a simpler and more clinically appealing technique compared to liquid-based delivery.…”

Section: Airway Surface Preparation Techniquesmentioning

confidence: 99%

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Effective viral-mediated lung gene therapy: is airway surface preparation necessary?

et al. 2022

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Gene-based therapeutics are actively being pursued for the treatment of lung diseases. While promising advances have been made over the last decades, the absence of clinically available lung-directed genetic therapies highlights the difficulties associated with this effort. Largely, progress has been hindered by the presence of inherent physical and physiological airway barriers that significantly reduce the efficacy of gene transfer. These barriers include surface mucus, mucociliary action, cell-to-cell tight junctions, and the basolateral cell membrane location of viral receptors for many commonly used gene vectors. Accordingly, airway surface preparation methods have been developed to disrupt these barriers, creating a more conducive environment for gene uptake into the target airway cells. The two major approaches have been chemical and physical methods. Both have proven effective for increasing viral-mediated gene transfer pre-clinically, although with variable effect depending on the specific strategy employed. While such methods have been explored extensively in experimental settings, they have not been used clinically. This review covers the airway surface preparation strategies reported in the literature, the advantages and disadvantages of each method, as well as a discussion about applying this concept in the clinic.

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Section: Airway Surface Preparation Techniquesmentioning

confidence: 99%

Section: Airway Surface Preparation Techniquesmentioning

confidence: 99%

Effective viral-mediated lung gene therapy: is airway surface preparation necessary?

et al. 2022

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Perfluorochemical Liquid Enhances Adeno-Associated Virus-Mediated Transgene Expression in Lungs

et al. 2000

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Use of adeno-associated virus (AAV) vectors for lung gene therapy is limited, in part, by low levels of AAV-mediated transgene expression in lungs. Generally, less than 1% of total airway and alveolar epithelial cells express transgene activity following vector administration. A means of improving AAV vector delivery could potentially enhance AAV-mediated gene expression in lungs. We have previously demonstrated that use of perfluorochemical (PFC) liquids improved overall levels of adenovirus vector-mediated gene expression as well as distribution of expression in lungs of spontaneously breathing rodents. To evaluate whether use of PFC liquids might similarly enhance AAV-mediated expression, spontaneously breathing rodents received intratracheal instillation of the AAV vectors CWRAP and ARAP4 (2-5 x 10(8) FFU/animal) with or without 10 cc/kg body wt PFC liquid (FC-75, ACROS). Animals were sacrificed 4 weeks later and lungs assessed for overall and in situ alkaline phosphatase (AP) expression. Animals receiving vector alone exhibited scattered sparse in situ activity, predominantly in alveolar epithelium. In contrast, animals receiving vector with FC-75 exhibited increased and more widespread AP expression as well as up to a 26-fold increase in AP activity. These results demonstrate that use of the PFC liquid FC-75 improves overall and in situ AAV-mediated gene expression in rodent lungs.

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Use of Perfluorochemical Liquid Allows Earlier Detection of Gene Expression and Use of Less Vector in Normal Lung and Enhances Gene Expression in Acutely Injured Lung

2001

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One of the obstacles to successful lung gene transfer is effective delivery of vector to lung, particularly injured or diseased lung. We have previously demonstrated that intratracheal instillation of perfluorochemical (PFC) liquids along with instillation of recombinant adenovirus and adeno-associated virus vectors, or with cationic liposome vectors, increased total lung gene expression and enhanced distribution of gene expression throughout the lung. To further explore the potential benefits of PFC liquid use, we evaluated the effect of PFC liquid instillation on several other aspects of adenovirus-mediated gene expression in lung. Use of PFC liquid resulted in earlier detection of gene expression and allowed the use of less vector to achieve expression comparable to that observed with the use of higher amounts of vector alone. Using PFC liquid also enhanced gene expression in a rodent model of acute lung injury. PFC liquid did cause a transient inflammation when instilled into normal lungs but did not cause any additional inflammation when instilled alone or with adenovirus vector into acutely injured lungs. Thus, PFC liquid may be a useful adjunct for clinical lung gene transfer, particularly for injured or diseased lungs.

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Perfluorochemical Liquid-Enhanced Adenoviral Vector Distribution and Expression in Lungs of Spontaneously Breathing Rodents

Cited by 33 publications

References 0 publications

Effective viral-mediated lung gene therapy: is airway surface preparation necessary?

Effective viral-mediated lung gene therapy: is airway surface preparation necessary?

Perfluorochemical Liquid Enhances Adeno-Associated Virus-Mediated Transgene Expression in Lungs

Use of Perfluorochemical Liquid Allows Earlier Detection of Gene Expression and Use of Less Vector in Normal Lung and Enhances Gene Expression in Acutely Injured Lung

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