Preclinical and Clinical Studies Employing RNA Interference as a Therapeutic for Respiratory Syncytial Virus (RSV) Infection in the Lung - RNA Interference from Biology to Therapeutics - page 310

Chapter 15
Preclinical and Clinical Studies Employing RNA
Interference as a Therapeutic for Respiratory
Syncytial Virus (RSV) Infection in the Lung
Amy R. Simon , Verena Karsten , Rachel Meyers , Jeff Cehelsky ,
Jared Gollob , Akshay Vaishnaw , and Sara Nochur
Abstract Here, we describe the rational design, preclinical, and clinical development
of a small interfering RNA (siRNA) directed against human respiratory syncytial
virus (RSV). Infection with RSV can cause significant morbidity in young children
and in elderly or immunosuppressed adults. In recipients of lung transplants, RSV
infection has been associated with early onset of bronchiolitis obliterans syndrome
(BOS), which leads to significant morbidity and mortality. Human studies included a
Phase II study in adults experimentally infected with RSV. In this study, ALN-RSV01
significantly reduced the rate of RSV infection and resulted in lower overall viral
loads and a shorter duration of viral shedding. In two subsequent Phase II studies,
ALN-RSV01 was administered as a nebulized aerosol to lung transplant patients
naturally infected with RSV. Safety and significant reduction in BOS was first
demonstrated in 16 patients. Results from a larger study in 87 patients are currently
pending. The approach for using a nebulized siRNA to treat a local lung pathogen is
exciting to the field, given the specificity that can be employed by RNA interference
technology, the minimal systemic exposure, and the potential to silence endogenous
and invading targets that impact lung function and lung diseases.
A. R. Simon ( * ) • V. Karsten • R. Meyers • J. Cehelsky • J. Gollob • A. Vaishnaw • S. Nochur
Alnylam Pharmaceuticals , 300 3rd Street , Cambridge , MA 02142 , USA
e-mail: [e-mail]