Critical considerations for developing nucleic acid macromolecule based drug products

• Published in: Drug discovery today Vol. 21; no. 3; pp. 430 - 444
• Main Authors: Muralidhara, Bilikallahalli K., Baid, Rinku, Bishop, Steve M., Huang, Min, Wang, Wei, Nema, Sandeep
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-03-2016
• Subjects: Drug Compounding; Drug Stability; Nucleic Acids - chemistry
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2015.11.012

•Increased emphasis in recent years on DNA/mRNA macromolecule-based therapeutic drugs.•Formulation excipients and their role in increasing the drug product stability are discussed.•Chemical liabilities, major degradation routes and characterization methods are reviewed.•Advanced formulations for some of the targeted delivery challenges are discussed.•Glossary of current clinical stage assets of nucleic-acid-based therapeutics is included.
Protein expression therapy using nucleic acid macromolecules (NAMs) as a new paradigm in medicine has recently gained immense therapeutic potential. With the advancement of nonviral delivery it has been possible to target NAMs against cancer, immunodeficiency and infectious diseases. Owing to the complex and fragile structure of NAMs, however, development of a suitable, stable formulation for a reasonable product shelf-life and efficacious delivery is indeed challenging to achieve. This review provides a synopsis of challenges in the formulation and stability of DNA/m-RNA based medicines and probable mitigation strategies including a brief summary of delivery options to the target cells. Nucleic acid based drugs at various stages of ongoing clinical trials are compiled.