Current prospects for gene therapy of cystic fibrosis

Abstract

Conventional therapy for cystic fibrosis has extended the median survival age, but the disease is still fatal. Gene therapy can correct the primary and secondary defects associated with cystic fibrosis, but limited extent and duration of the corrections as well as concerns about the safety of some current delivery systems have prevented gene therapy from being curative. For viral vectors, the main challenges are access to target cells and host immunity, which prevents efficient re-administration. Masking viral particles from the immune system, the use of alternative serotypes, or retargeting have been employed to address these issues. Non-viral vectors have dramatically improved over the past five years but improvements in efficacy are needed. In lung, naked DNA has been inefficient and lipid-based vectors have only achieved efficient gene transfer at doses that elicit limiting inflammatory responses. Molecular conjugates or polymer-based delivery overcomes some limitations, with good ability to transfect non-dividing cells. Improvements of viral and non-viral vectors continue to advance the construction of stable, safe and efficacious vectors that can be re-administered.