Biomaterials for mRNA delivery

Abstract

Messenger RNA (mRNA) has recently emerged with remarkable potential as an effective alternative to DNA-based therapies because of several unique advantages. mRNA does not require nuclear entry for transfection activity and has a negligible chance of integrating into the host genome which excludes the possibility of potentially detrimental genomic alternations. Chemical modification of mRNA has further enhanced its stability and decreased its activation of innate immune responses. Additionally, mRNA has been found to have rapid expression and predictable kinetics. Nevertheless, the ubiquitous application of mRNA remains challenging given its unfavorable attributes, such as large size, negative charge and susceptibility to enzymatic degradation. Further refinement of mRNA delivery modalities is therefore essential for its development as a therapeutic tool. This review provides an exclusive overview of current state-of-the-art biomaterials and nanotechnology platforms for mRNA delivery, and discusses future prospects to bring these exciting technologies into clinical practice.

Charge-altering releasable transporters (CARTs) for the delivery and release of mRNA in living animals

“…Recently, preclinical development of materials specific for mRNA delivery has resulted in cationic polymers such as polymethacrylates (27)(28)(29), poly(aspartamides) (30,31), and polypeptides (32), as well as multicomponent cationic lipid or lipid-like formulations (21,(33)(34)(35)(36). In many of these examples, however, transfection efficiencies can be quite low, ranging 20-80% in cells (18), with likely much lower efficiencies in vivo, which requires either high mRNA doses or hydrodynamic injections (32,37).…”

“…Despite this being a rapidly emerging subject of intense interest, relatively few classes of materials have been evaluated as mRNA delivery vehicles (14,18). Those that have emerged are largely inspired by or directly repurposed from DNA and siRNA delivery methods.…”

Delivery of modified mRNA encoding vesicular stomatitis virus matrix protein for colon cancer gene therapy

“…18,20,21 As a result, substantial modications have been invested to optimizing the structural of IVT mRNA including 5 0 cap, 5 0 -and 3 0 -UTRs, the coding region, and the poly(A) tail. 11 These efforts have overcome the aforementioned shortcomings with improved intracellular stability and translational efficiency. 22,23 Nowadays, IVT mRNA has undergone extensive clinical or pre-clinical investigation in the elds of therapeutic cancer vaccination, 24-27 cell programming [28][29][30] and so on, demonstrating great potential.…”

“…11 In vitro transcribed messenger RNA (IVT mRNA) has been applied as an alternative therapeutic molecule to plasmid DNA in the eld of cancer immunotherapy and stem cell-based biomedical research.…”

A mini review highlights on the application of nano-materials for Kidney disease: A key development in Medicinal therapy

“…Clinical trials have begun for the investigation of hafnium oxide NPs (phase I), which will be used as radio-sensitizers in patients with soft-tissue sarcomas [58]. Nano-medicines are also undergoing clinical translation for gene therapy [65], RNA interference [66][67][68], and immunotherapy [69][70]. Viral NPs have found utility in the delivery of a range of therapeutics and have been clinically confirmed for gene therapy applications [71][72][73].…”