Chantelle Carpentieri

Chantelle Carpentieri

Higher Degree by Research Candidate

Adelaide Medical School

Faculty of Health and Medical Sciences


PhD candidate at the University of Adelaide. Member of the Cystic Fibrosis Airway Research Group (CFARG) at the Women's and Children's Hospital, North Adelaide.

I am a PhD student working with the Adelaide Cystic Fibrosis Airway Research Group at the Women's and Children's Hospital. The aim over aim of my research project is to improve airway gene transfer levels by overcoming the extra- and intra- cellular barriers of the lung. 

Supported by: MS McLeod PhD Scholarship and CFSA top-up scholarship. 

Academic Background:

From 2014 to 2016 I studied a Bachelor of Biomedical Science at the University of Adelaide were I majored in Genetics and Microbiology & Virology. In 2017 I completed my honours in airway gene therapy for the treatment of CF lung disease. My honours project involved the comparison between two pseudotypes (VSV-G and HA) to determine which envelope protein produces higher levels of reporter gene expression in the lung over time following lentiviral gene delivery. After completing my honours I was offered a PhD position with the CF airway research group supervised by Associate professor Dr David Parsons, Dr Martin Donnelley and Dr Nigel Farrow. 

Research Project Background:

Airway gene therapy is currently under active development for the treatment of cystic fibrosis (CF) airway disease. A gene-addition therapy employs a gene vector (either viral or non-viral) to delivery functional copies of the CFTR gene to the relevant airway cells, with the ultimate goal of correcting the genetic cause of the disease for all patients with CF. While access to the lung is easy, the respiratory epithelium presents many challenges for efficient airway gene transfer. The lung has evolved a complex series of physical, anatomical and immune barriers to protect itself against foreign invaders such as bacteria and viruses. These natural barriers are also directed against gene transfer agents and therefore play a significant role in limiting efficient gene transfer in vivo. These hurdles to achieving efficient viral gene transfer include the paucity of viral receptors on the apical membrane surface, presence of epithelial tight junctions that prevent vector particles access to the basolateral receptors and the potent immune responses directed against the gene vector and/or transgenes. 

Lentiviral (LV) vectors are currently one of the leading viral vector candidates to deliver transgene to the airway epithelium. LVs offer many natural advantages such as the ability to transduce both dividing and non-dividing cells, large genetic carrying capacity, low immunogenicity and integrate into the host cell genome. To overcome some of the barriers to efficient viral mediated gene transfer, research has focused on investigating alternative pseudotypes (envelope proteins), the use of airway conditioning compounds such as lysophosphatidylcholine (LPC) and effective dosing strategies to overcome the immune system. My research project aims are:

1. Does altering the vector pseudotype improve airway gene transduction levels in vivo?

2. Is airway conditioning with LPC required in the lung as it is in the nasal epithelium and does it improve basal cell transduction?

3. Does multi-doses of a LV vector increase gene transductions levels and duration and can we effectively repeat administer with either the same or different transgenes if gene expression wanes?

 

 

 

   

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  • Journals

    Year Citation
    2021 Carpentieri, C., Farrow, N., Cmielewski, P., Rout-Pitt, N., McCarron, A., Knight, E., . . . Donnelley, M. (2021). The Effects of Conditioning and Lentiviral Vector Pseudotype on Short- and Long-Term Airway Reporter Gene Expression in Mice. HUMAN GENE THERAPY, 32(15-16), 817-827.
    DOI Scopus1 WoS1
  • Conference Items

    Year Citation
    2018 Carpentieri, C., Farrow, N., Mcintyre, C., Cmielewski, P., Rout-Pitt, N., Parsons, D., & Donnelley, M. (2018). COMPARATIVE EFFICIENCY OF HA AND VSV-G PSEUDOTYPED LENTIVIRAL VECTORS FOR CYSTIC FIBROSIS AIRWAY GENE THERAPY. Poster session presented at the meeting of RESPIROLOGY. WILEY.
    2018 Carpentieri, C., Farrow, N., Cmielewski, P., McIntyre, C., McCarron, A., Rout-Pitt, N., . . . Donnelley, M. (2018). Airway Gene-Addition Therapy for Cystic Fibrosis: the VSV-G Pseudotype Produces Higher Transduction Levels Than HA. Poster session presented at the meeting of MOLECULAR THERAPY. Chicago, IL: CELL PRESS.
    2017 Carpentieri, C. L., Farrow, N., McIntyre, C., McCarron, A., Rout-Pitt, N., Parsons, D., & Donnelley, M. (2017). COMPARATIVE EFFICIENCY OF HA AND VSV-G PSEUDOTYPED LENTIVIRAL VECTORS DEVELOPED FOR TREATING CYSTIC FIBROSIS LUNG DISEASE. Poster session presented at the meeting of PEDIATRIC PULMONOLOGY. WILEY.

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