Recent advances in polymeric materials for the delivery of RNA therapeutics

ABSTRACT

Introduction: The delivery of nucleic acid therapeutics through non-viral carriers face multiple biological barriers that reduce their therapeutic efficiency. Despite great progress, there remains a significant technological gap that continues to limit clinical translation of these nanocarriers. A number of polymeric materials are being exploited to efficiently deliver nucleic acids and achieve therapeutic effects.

Areas covered: We discuss the recent advances in the polymeric materials for the delivery of nucleic acid therapeutics. We examine the use of common polymer architectures and highlight the challenges that exist for their development from bench side to clinic. We also provide an overview of the most notable improvements made to circumvent such challenges, including structural modification and stimuli-responsive approaches, for safe and effective nucleic acid delivery.

Expert opinion: It has become apparent that a universal carrier that follows ‘one-size’ fits all model cannot be expected for delivery of all nucleic acid therapeutics. Carriers need to be designed to exhibit sensitivity and specificity toward individual targets diseases/indications, and relevant subcellular compartments, each of which possess their own unique challenges. The ability to devise synthetic methods that control the molecular architecture enables the future development that allow for the construction of ‘intelligent’ designs.

Graphical Abstract

KEYWORDS:

• mRNA delivery
• siRNA delivery
• RNA therapeutics
• nucleic acid delivery
• lipid and polymeric nanoparticles
• delivery materials

Article highlights

• Success in RNA-based therapeutics require delivery systems with properties that achieve efficient cellular targeting and internalization as well as the release of nucleic acid cargo into the cytosol.

• Polymeric materials are emerging as an attractive alternative to lipid nanoparticles for the delivery of RNA therapeutics. This is especially true for extrahepatic delivery-based applications.

• Polymeric materials can be created by tuning the physiochemical characteristics needed for efficient delivery, while maintaining high loading capacity and low immunogenicity.

• Stimuli-responsiveness within polymer architectures (a triggered conformational change or bond cleavage) permits a programmed, specific delivery of nucleic acids to target sites which can improve both transfection efficiency and biocompatibility.

• A ‘one-size’ fit all model cannot be expected for the delivery of all RNA therapeutics. Carriers need to be designed to exhibit sensitivity and specificity toward individual targets diseases/indications, and relevant subcellular compartments, each of which possess their own unique challenges.

• Different strategies in ‘intelligent’ polymeric design can be used to enhance cellular uptake, endosomal escape, and the release of nucleic acids from their carriers.

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Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

D Ulkoski is supported by the AstraZeneca Postdoc programme.