Extracellular barriers in respiratory gene therapy.
Respiratory gene therapy has been considered for the treatment of a broad range of pulmonary disorders. However, respiratory secretions form an important barrier towards the pulmonary delivery of therapeutic nucleic acids. In this review we will start with a brief description of the biophysical properties of respiratory mucus and alveolar fluid. This must allow the reader to gain insights into the mechanisms by which respiratory secretions may impede the gene transfer efficiency of nucleic acid containing nanoparticles (NANs). Subsequently, we will summarize the efforts that have been done to understand the barrier properties of respiratory mucus and alveolar fluid towards the respiratory delivery of therapeutic nucleic acids. Finally, new and current strategies that can overcome the inhibitory effects of respiratory secretions are discussed.
Sanders
Niek
N
Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium. Niek.Sanders@UGent.be
Rudolph
Carsten
C
Braeckmans
Kevin
K
De Smedt
Stefaan C
SC
Demeester
Joseph
J
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004058:Diffusion; D005100:Expectorants / Q000008:administration & dosage / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008171:Lung Diseases / Q000628:therapy; D008954:Models, Biological; D009093:Mucus / Q000737:chemistry / Q000502:physiology*; D053758:Nanoparticles / Q000008:administration & dosage; D009696:Nucleic Acids / Q000008:administration & dosage; D020545:Respiratory Mucosa / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D013183:Sputum / Q000737:chemistry / Q000378:metabolism
D005100:Expectorants; D009696:Nucleic Acids