Exosomes for mRNA delivery: a novel biotherapeutic strategy with hurdles and hope

Abstract

Over the past decade, therapeutic messenger RNAs (mRNAs) have emerged as a highly promising new class of drugs for protein replacement therapies. Due to the recent developments, the incorporation of modified nucleotides in synthetic mRNAs can lead to maximizing protein expression and reducing adverse immunogenicity. Despite these stunning improvements, mRNA therapy is limited by the need for the development of safe and efficient carriers to protect the mRNA integrity for in vivo applications. Recently, leading candidates for in vivo drug delivery vehicles are cell-derived exosomes, which have fewer immunogenic responses. In the current study, the key hurdles facing mRNA-based therapeutics, with an emphasis on recent strategies to overcoming its immunogenicity and instability, were highlighted. Then the immunogenicity and toxicity of exosomes derived from various cell sources were mentioned in detail. Finally, an overview of the recent strategies in using exosomes for mRNA delivery in the treatment of multiple diseases was stated.

Low-Power Sonication Can Alter Extracellular Vesicle Size and Properties

“…In a recent study, an EV-based antibody array profiling identified CD151, CD171, and Tetraspanin 8 among the most significant molecules to differentiate histological lung cancer patients from cancer-free individuals [8]. EVs are also considered a potential therapeutic resource as a drug cell delivery vector based on their efficient cellular uptake [6,7,9,10], as recently illustrated by intravenous administration of engineered EVs loaded with curcumin able to target an ischemic brain lesion in rodents [11].…”

The Emerging Role of Ionic Liquid-Based Approaches for Enhanced Skin Permeation of Bioactive Molecules: A Snapshot of the Past Couple of Years

“…Interestingly, when looking at the forefront of VNs-mediated drug delivery, we can witness the increasing relevance of cell-based VNs such as exosomes [ 59 ] or outer membrane vesicles (OMVs) from Gram-negative bacteria [ 60 ], whose major hallmark is their expectedly high biocompatibility and low immunogenicity. Exosomes are extracellular vesicles that integrate proteins and nucleic acids of their secreting cells, and which can affect function and properties of other cells able to internalize them [ 59 ]; as such, recent efforts address their engineering for targeted drug delivery [ 61 , 62 ], also for diverse dermatological applications [ 63 , 64 , 65 ] and wound healing [ 66 ]. Besides exosomes, OMVs are also becoming prominent actors in several biomedical applications, including recent examples where engineered OMVs from transgenic Escherichia coli have been used for DTD of biopharmaceuticals, alone [ 60 ] or in combination with phototherapy [ 67 ].…”

mRNA Therapeutic Modalities Design, Formulation and Manufacturing under Pharma 4.0 Principles

“…Another promising delivery tool for therapeutic mRNAs could be exosomal delivery [ 177 , 178 ]. Given that exosomes play a pivotal role in mRNA transfer between cells and have membrane permeability properties, they could be an optimal delivery system for mRNAs.…”