Introduction
Lately, messenger RNA (mRNA) has proven nice therapeutic potential in biomedical purposes as a consequence of its potential to immediately categorical goal protein as soon as enters the host cells [1], [2], [3], [4]. On account of its benefits of excessive security, fast improvement and scalable manufacturing, mRNA-based therapies have emerged as a promising device for gene remedy and vaccine improvement [5], [6], [7], [8]. As a result of inherent susceptibility to enzymatic degradation and poor cell penetration, mRNA molecules require steady and efficient supply techniques to offer safety towards enzymatic assault and facilitate entrance to focus on cells [9], [10]. Nonetheless, the preparation of secure, efficient and controllable supply techniques remains to be one of many greatest challenges for medical software of mRNA therapeutics.
To date, a wide range of nanomaterials have been explored for mRNA supply, together with protein-based techniques, polymer-based techniques and lipid-based techniques [11], [12]. Significantly, lipid nanoparticle (LNP) has been principally investigated and efficiently accredited for medical use because of the good biocompatibility and controllable physicochemical properties [13], [14]. Within the present techniques, the cationic or ionizable lipids are important for encapsulating the negatively charged mRNA into LNPs by compacting the versatile lengthy mRNA strands by way of electrostatic interactions [15], [16]. Whereas the utilization of cationic lipids can provide the excessive mRNA encapsulation ef?ciency, the extreme optimistic expenses could result in non-specific binding with plasma proteins in vivo, inflicting cytotoxicity and antagonistic immune responses [17], [18], [19], [20]. Though the event of ionizable lipids has partially scale back the toxicity of cationic lipids, they could additionally end result within the long-term instability and brief shelf lifetime of the LNPs [21], [22], [23]. Due to this fact, it’s nonetheless an ideal problem to discover new cationic lipid-independent technique to encapsulate mRNA into LNP, which is important to develop novel supply system with versatile lipids for mRNA.
Herein, we proposed a cationic lipid-independent technique to organize LNPs encapsulating mRNA (mRNA-LNPs), as illustrated in Fig. 1. In our research, profiting from the endogenous secondary constructions of mRNA, a basic compacting technique was designed, which allowed the mRNA to self-fold into compact mRNA particles (ComRNPs). Primarily based on the frame-guided meeting (FGA) technique [24], [25], [26], [27], main hydrophobic teams (LHGs) have been anchored on the ComRNPs to type the mRNA amphiphilic frames, which might subsequently information the phospholipids to type vesicles. Our technique provided a novel and versatile device to encapsulate mRNA into LNPs with non-ionic interactions, benefiting additional improvement for mRNA therapeutic purposes.