Polyester materials for mRNA delivery

Abstract

Messenger RNA (mRNA) has recently made important progress in clinical implementation, offering a promising therapeutic option for infectious disease and cancer. However, the nature of mRNA molecules rendered them poorly bioavailable and unstable in vivo, impeding their further clinical application. Therefore, safe and efficient delivery of mRNA therapeutics to the target site is crucial for their successful translation into the clinical setting. Various vectors have been explored for mRNA delivery. Among them, polyesters and their analogs, a family of biodegradable polymers, have exhibited great potential for mRNA delivery. In this short review, the authors briefly introduce mRNA therapeutics, their therapeutic applications and delivery challenges. The authors then presented the typical examples of polyester materials for mRNA delivery to highlight the current progress and discuss the challenges for the rational design of polyester based mRNA delivery vectors. The authors hope to provide a new insight for the design of biodegradable vectors for nucleic acids delivery, thereby promoting their further clinic translation.

mRNA Delivery: Challenges and Advances through Polymeric Soft Nanoparticles

“…They are hydrolysed in biological media to non-toxic products that can be cleared through the renal filtration. Polylactic acid (PLA), polyglycolic acid (PGA), poly (D, L-lactide-coglycolide) (PLGA), polycaprolactone (PCL), and poly (β-hydroxybutyric acid) are common polyesters used for nucleic acid delivery [129]. They are generally synthesized through polycondensation or ring-opening polymerization.…”

Advances in non-viral mRNA delivery to the spleen

“…However, the degradability of the ester bond may pose a disadvantage for polyesters as the stability of these polymeric nanoparticles in human serum may be limited. 147 Polyester structural modifications have been explored as one strategy to prevent rapid degradation upon administration. 148,149 To improve the transfection efficiency of polyesters and promote splenic uptake of polyester-based polymers, the Waymouth group has developed charge-altering releasable transporters (CARTs).…”

Rational design of polymer-based mRNA delivery systems for cancer treatment

“…Polyester with functional groups can deliver mRNA therapeutics specifically into immune cells to induce a strong immune response. 75 However, a series of technical challenges need to be overcome to effectively encapsulate mRNA in polyesters. Due to the significant differences between mRNA and polyesters, such as hydrophobicity/hydrophilicity, this leads to repulsion problems when they come into contact with each other.…”