The Anatomy of a Virus: Active Research Projects in the Croyle Lab

To date, viral vectors have held the most promise as vehicles for gene therapy because they are capable of delivering genes to certain tissues with high efficiency and establishing stable transgene expression for significant periods of time. However, routine use of viruses for therapeutic purposes is significantly limited by the innate immune response against capsid proteins, viral gene products and the therapeutic transgene. Recombinant viral preparations must also be extremely pure for clinical use. In this form, however, they often exhibit poor physical stability. Research in my laboratory focuses on the development of methods to reduce the immune response and associated toxicity associated with recombinant viruses and methods to evaluate the physical stability of viral vectors during processing and purification. The primary vectors under investigation are adenoviruses, adeno-associated viruses and lentiviruses. Students in my lab are exposed to cutting edge, interdisciplinary research relevant to the fields of cell biology, virology and immunology, with basic skills in pharmaceutics and drug delivery also emphasized. Projects address basic research problems and sharpen skills in hypothesis development and open-ended problem solving. Application of research techniques to clinical settings is also emphasized. Specific projects are

  •  Biochemical Modification of Viruses to Evade the Immune Response

  •  Effect of Recombinant Viruses on Hepatic, Renal and Intestinal Drug Metabolism

  •  Vaccination Strategies for Rapid Induction of Immunity Against Dangerous Pathogens

  •  Production, Processing & Physical Stability of Recombinant Viruses

A Long-Lasting, Single-Dose Nasal Vaccine for Ebola: A Practical Armament for an Outbreak with Significant Global Impact.  2015.  Expert Review of Anti-infective Therapy 2015 13:5 , 527-530.

Bolstering Components of the Immune Response Compromised by Prior Exposure to Adenovirus: Guided Formulation Development for a Nasal Ebola Vaccine.   2015.  Mol. Pharm. 12 (8):2697–2711.

A Single Dose Respiratory Recombinant Adenovirus-Based Vaccine Provides Long-Term Protection for Non-Human Primates from Lethal Ebola Infection.  2015.  Mol. Pharm. 12 (8):2712–2731. 

Evaluation of the HC-04 Cell Line as an In Vitro Model for Mechanistic Study of Changes in the Function of CYP3A During Virus Infection. (2014)  Drug Metab. Dispos. 42(7):1191-1201.

Modeling Pre-Existing Immunity to Adenovirus in Rodents: Immunological Requirements for Successful Development of a Recombinant Adenovirus Serotype 5-Based Ebola Vaccine. (2013) Mol. Pharm. 10(9):3342-3355.

 A PEGylated Helper-Dependent Adenoviral Vector ExpressingHuman Apo-A1 Reduces Atherosclerosis in LDLR Deficient Mice. (2013) Gene Ther. 20(12):1124-1130.

 Emerging Targets and Novel Approaches to Ebola Virus Prophylaxis and Treatment. (2013) BioDrugs, 27(6), 565-583.

 A single sublingual dose of an adenovirus-based vaccine protects against lethal Ebola challenge in mice and guinea pigs. (2012) Mol. Pharm. 9(1), 156-167.

 Pharmacology and Toxicology of PEGylated Helper-Dependent Adenoviruses in Non-Human Primates. (2011) Mol. Pharm. 7(8), 78-92.

Development of a Nasal Adenovirus-Based Ebola Vaccine: Effect of Concentration and Formulation on Adenovirus Stability and Infectious Titer during Actuation from Two Intranasal Delivery Devices. (2010) Vaccine 28(9), 2137-2148.

Long-Term Virus-Induced Alterations of CYP3A-Mediated Drug Metabolism: A Look at the Virology, Immunology and Molecular Biology of A Multi-Faceted Problem (2009) Expert Opin. Drug Metab. Toxicol. 5(10), 1189-211.

Drug-virus interaction: effect of administration of recombinant adenoviruses on the pharmacokinetics of docetaxel in a rat model. (2009) Cancer Gene Ther. 16(5), 405-14.

Enhanced protection against Ebola virus mediated by an improved adenovirus-based vaccine. (2009) PLoS One 4(4), e5308.

Molecular and macromolecular alterations of recombinant adenoviral vectors do not resolve changes in hepatic drug metabolism during infection. (2008) Virol. J. 5, 111.

Nasal delivery of an adenovirus-based vaccine bypasses pre-existing immunity to the vaccine carrier and improves the immune response in mice. (2008) PLoS One 3(10), e3548.

Mucosal Delivery of Adenovirus-Based Vaccine Protects against Ebola Virus Infection in Mice (2007) J Infect Dis 196, S413-42