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Inhaled RNA Therapy: Challenges and Opportunities

Lam JK.

Respiratory Drug Delivery 2021. Volume , 2021: 109-116.

Abstract:

Ribonucleic acid (RNA), especially small interfering RNA (siRNA) and messenger RNA (mRNA), hold great promise for the treatment of lung diseases including viral lung infections, cystic fibrosis and severe asthma. Inhaled dry powder formulations are attractive due to their ease of administration, yet the notoriously unstable RNA molecules render their creation a big challenge. In this paper, two particle engineering techniques, namely spray drying and spray freeze drying, were examined for the preparation of inhalable RNA dry powders. We showed that the appropriate use of excipients (e.g., L-leucine and human serum albumin) and the manipulation of processing parameters (e.g., atomization gas flow rate) could influence the aerosol performance of the formulations. We further demonstrated in vivo RNA transfection in the lungs of animals following pulmonary delivery of RNA powder aerosol, taking inhaled RNA therapy, including mRNA vaccination, one step closer to clinical application.