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Preclinical and Clinical Studies Employing RNA Interference as a Therapeutic for Respiratory Syncytial Virus (RSV) Infection in the Lung

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RNA Interference from Biology to Therapeutics

Part of the book series: Advances in Delivery Science and Technology ((ADST))

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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.

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Authors and Affiliations

  1. Alnylam Pharmaceuticals, 300 3rd Street, Cambridge, MA, 02142, USA

    Amy R. Simon, Verena Karsten, Rachel Meyers, Jeff Cehelsky, Jared Gollob, Akshay Vaishnaw & Sara Nochur

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  1. Amy R. Simon
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  2. Verena Karsten
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  3. Rachel Meyers
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  4. Jeff Cehelsky
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  6. Akshay Vaishnaw
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  7. Sara Nochur
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Correspondence to Amy R. Simon .

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  1. Interdisciplinary Nanoscience Center, Aarhus University, Ny Munkegade 118, Aarhus, 8000 AA, Denmark

    Kenneth A. Howard

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Simon, A.R. et al. (2013). Preclinical and Clinical Studies Employing RNA Interference as a Therapeutic for Respiratory Syncytial Virus (RSV) Infection in the Lung. In: Howard, K. (eds) RNA Interference from Biology to Therapeutics. Advances in Delivery Science and Technology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-4744-3_15

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