Tackling Stability and Delivery Challenges in Commercial Nucleic Acid Therapeutics

Mantripragada Yosipovitch^*
*Correspondence: Mantripragada Yosipovitch, Department of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia Str., 020956 Bucharest, Romania, Email:

Introduction

Nucleic acid therapeutics hold immense promise in revolutionizing medicine by targeting diseases at their genetic roots. However, realizing this potential requires overcoming significant hurdles, particularly concerning stability and delivery. In this article, we delve into the challenges faced in commercializing nucleic acid therapeutics and explore innovative strategies to tackle them effectively. Nucleic acid therapeutics, including RNA interference (RNAi), Antisense Oligonucleotides (ASOs) and messenger RNA (mRNA) therapeutics, offer highly specific and potent mechanisms for treating a wide array of diseases, ranging from genetic disorders to cancers and infectious diseases. By precisely modulating gene expression or protein production, these therapeutics hold the potential to provide personalized treatments with minimal off-target effects. One of the primary challenges in commercializing nucleic acid therapeutics is ensuring their stability. These molecules are inherently prone to degradation by nucleases, enzymes that break down nucleic acids. Moreover, challenges arise during manufacturing, storage and delivery, where exposure to various environmental factors can compromise their integrity [1].

Nucleases present in biological fluids, such as serum and cytoplasm, can rapidly degrade nucleic acid therapeutics, limiting their efficacy and bioavailability. Strategies to combat this include chemical modifications to enhance stability and the development of delivery systems that protect nucleic acids from enzymatic degradation. Ensuring the stability of nucleic acid therapeutics during manufacturing is crucial for maintaining their efficacy and safety. Optimizing production processes and implementing quality control measures are essential to minimize degradation and ensure batch-to-batch consistency. Proper storage conditions are critical to preserving the integrity of nucleic acid therapeutics over time. Factors such as temperature, humidity and light exposure can affect stability, necessitating the development of stable formulations and packaging solutions. In addition to stability concerns, effective delivery of nucleic acid therapeutics to target cells or tissues remains a significant obstacle. These molecules face barriers such as cellular membranes, immune responses and off-target effects, which must be overcome to achieve therapeutic outcomes [2].

Description

Nucleic acids must cross cellular membranes to reach their intracellular targets. Various delivery systems, including lipid nanoparticles, polymerbased carriers and viral vectors, are being developed to enhance cellular uptake and intracellular trafficking. Nucleic acid therapeutics can trigger immune responses, leading to inflammation and potential adverse effects. Engineering nucleic acids with reduced immunogenicity and incorporating immunomodulatory agents into delivery systems can mitigate immune activation and improve safety profiles. Unintended interactions of nucleic acids with non-target molecules can result in off-target effects, limiting their therapeutic specificity. Rational design approaches and screening methodologies are employed to minimize off-target binding and enhance selectivity.

Addressing stability and delivery challenges in commercial nucleic acid therapeutics requires interdisciplinary collaboration and continuous innovation. Advances in chemical synthesis, formulation science and nanotechnology are driving the development of novel solutions to enhance the stability, delivery and efficacy of these therapeutics. Engineering advanced delivery systems with improved targeting capabilities, controlled release mechanisms and enhanced biocompatibility holds promise for overcoming delivery barriers and optimizing therapeutic outcomes [3].

Precision Medicine Approaches: Leveraging genomic and transcriptomic data to tailor nucleic acid therapeutics to individual patients' genetic profiles can enhance efficacy and minimize adverse effects, advancing the paradigm of precision medicine. Establishing robust regulatory frameworks that account for the unique characteristics of nucleic acid therapeutics is essential for expediting their translation from bench to bedside. Collaboration between regulatory agencies, industry stakeholders and academic researchers is crucial for streamlining the development and approval processes. Tackling stability and delivery challenges is paramount to realizing the full therapeutic potential of nucleic acid-based medicines. Through innovative approaches, interdisciplinary collaboration and rigorous regulatory oversight, the field is poised to overcome these hurdles and usher in a new era of precision medicine, where tailored nucleic acid therapeutics offer hope for patients with previously untreatable diseases. Bioconjugation strategies involve attaching nucleic acids to various carriers or targeting ligands to improve stability and enhance delivery. By conjugating nucleic acids with molecules such as peptides, antibodies, or small molecules, researchers can increase their circulation time, target specific cell types and overcome biological barriers [4].

Exosomes, naturally occurring extracellular vesicles secreted by cells, have emerged as promising vehicles for delivering nucleic acid therapeutics. These nanoscale vesicles possess inherent stability, biocompatibility and the ability to traverse biological barriers, making them attractive candidates for drug delivery. Harnessing exosomes as delivery vehicles for nucleic acids holds potential for achieving targeted and sustained therapeutic effects with reduced immunogenicity. By subjecting nucleic acid libraries to selective pressures within biological systems, researchers can identify sequences that exhibit optimal stability, cellular uptake and target specificity, facilitating the development of improved therapeutics. Recent advancements in genome editing technologies, such as CRISPR-Cas systems, offer new opportunities for nucleic acid therapeutics. By precisely editing or modulating gene expression at the DNA level, these technologies enable targeted correction of genetic mutations underlying inherited diseases. Integration of nucleic acid therapeutics with genome editing tools holds promise for developing curative treatments for genetic disorders with high specificity and efficacy [5].

Conclusion

The integration of smart materials and nanotechnology holds immense potential for enhancing the stability, delivery and functionality of nucleic acid therapeutics. Engineered nanomaterials, such as mesoporous silica nanoparticles, polymer micelles and dendrimers, can serve as versatile platforms for encapsulating and delivering nucleic acids with controlled release kinetics and targeting capabilities. Furthermore, the development of stimuli-responsive materials that undergo conformational changes or release cargo in response to specific biological cues offers opportunities for designing tailored delivery systems with enhanced efficacy and safety. Accelerating the clinical translation and commercialization of nucleic acid therapeutics requires strategic partnerships between academia, industry and regulatory agencies. Collaborative efforts to optimize manufacturing processes, establish scalable production platforms and conduct rigorous preclinical and clinical evaluations are essential for advancing promising candidates towards regulatory approval and market availability. Additionally, innovative business models, intellectual property strategies and reimbursement frameworks are needed to incentivize investment in nucleic acid-based drug development and ensure access to these transformative therapies for patients worldwide.

Acknowledgement

None.

Conflict of Interest

There are no conflicts of interest by author.

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