Poster Presentation 2014 International Biophysics Congress

Biodegradable DNA nanoparticles for efficient in vivo thymulin gene delivery in experimental chronic allergic inflammation (#369)

Adriana L. da Silva 1 , Panagiotis Mastorakos 2 , Jung Soo Suk 2 , Justin Hanes 2 , Patricia R.M. Rocco 1 , Marcelo M. Morales 1
  1. Federal University of Rio de Janeiro, Rio De Janeiro, RJ, Brazil
  2. Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA

Introduction: Asthma is a chronic disease characterized by airway inflammation. However, the current available therapies are, in many circumstances, ineffective or induce side effects when chronically administered, such as corticosteroids. We evaluated the effects of thymulin gene therapy delivered by a novel biodegradable platform in experimental asthma. Poly (β-amino ester) polymers (PBAE), in particular, provide a non-toxic, biodegradable polymer library for the compaction of DNA, offering highly effective gene delivery. Moreover, the subtle variations in the polymer backbone and end-capping groups offer cell type specific transgene expression1.

Results: These polymers were synthetized, particles were formulated and characterized. The transfection efficacy was performed in vivo and in vitro. Nanoparticle diffusivity was accessed in lung mucus by multiple particles tracking method. Balb/c mice were sensitized and challenged with ovalbumin (OVA). Twenty-four hours after the last challenge, thymulin (100ug DNA) or saline were intratracheally instilled. After 24 h, animals were sacrificed and lung histology analyzed. DNA nanoparticles exhibited a near neutral surface charge (–1.5 ± 3.9 mV), and hydrodynamic diameter was 45.6 ± 2.6 nm (PDI ~0.1). The particles exhibited significant transfection efficiency. Particles displayed time-lapse trajectories that spanned greater distances compared to commonly used particles. In OVA mice, thymulin particleswere effective at reducing inflammation.

Conclusion: In the present model of chronic allergic asthma, the use of thymulin gene therapy delivered by a novel platform was effective in reducing the inflammatory process in lung.

Supported by: CNPq, CAPES, FAPERJ, NIH

  1. Akinc, A., et al., Bioconjug Chem, 2003.