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. 2023 Jul 7;22:106. doi: 10.1186/s12943-023-01807-w

Table 2.

Characteristics of mRNA cancer vaccine delivery methods

Delivery Method Description Mechanism of Action Advantages Disadvantages Safety Concerns Clinical Development Status Potential Applications Reference
In vivo injection of naked mRNA Direct injection of mRNA into the patient Expression of the antigen by host cells Simple and low cost Low transfection efficiency and immunogenicity Inflammation at the injection site Preclinical and early clinical trials Melanoma, prostate cancer, infectious diseases [61]
Lipid nanoparticles (LNPs) mRNA encapsulated in a lipid nanoparticle for delivery Facilitate cellular uptake and mRNA release High transfection efficiency and immunogenicity Potential toxicity and accumulation in liver Immune response to the lipid components Clinical trials ongoing Various cancer types, infectious diseases [128]
Electroporation Electrical pulse applied to cells to increase permeability Enhance mRNA delivery and uptake High transfection efficiency and immunogenicity Pain and muscle contractions Electrode burn and tissue damage Early clinical trials Melanoma, breast cancer, head and neck cancer [129]
Dendritic cell loading mRNA loaded into dendritic cells (DCs) for antigen presentation Increase antigen presentation and T cell activation Efficient and targeted delivery Complex and costly production process DC maturation and activation Preclinical and early clinical trials Various cancer types [130]
Polymeric nanoparticles mRNA encapsulated in a polymeric nanoparticle for delivery Facilitate cellular uptake and mRNA release Biodegradable and biocompatible Lower transfection efficiency than LNPs Potential toxicity and accumulation in liver Preclinical trials Various cancer types, infectious diseases [131]
Protamine-condensed mRNA mRNA condensed with protamine for delivery Facilitate cellular uptake and mRNA release Efficient and low cost High toxicity and immunogenicity Non-specific activation of immune cells Preclinical trials Various cancer types, infectious diseases [132]
mRNA-coated gold nanoparticles mRNA adsorbed onto gold nanoparticles for delivery Facilitate cellular uptake and mRNA release Efficient and targeted delivery Potential toxicity and accumulation in liver Gold nanoparticles may activate immune cells Preclinical trials Various cancer types, infectious diseases [133]
In vitro transcribed mRNA-loaded exosomes mRNA loaded into exosomes for delivery Facilitate cellular uptake and mRNA release Targeted delivery and high stability Lower transfection efficiency than LNPs Immunogenicity of the exosomes Preclinical trials Various cancer types [66]
Synthetic polymeric vectors mRNA encapsulated in a synthetic polymeric vector for delivery Facilitate cellular uptake and mRNA release Biocompatible and biodegradable Lower transfection efficiency than LNPs Potential toxicity and accumulation in liver Preclinical trials Various cancer types [134]
Self-amplifying mRNA vaccines mRNA encoding self-replicating RNA for delivery Amplification of mRNA expression in vivo High immunogenicity and long-term antigen expression Potential toxicity and long-term safety concerns Immune response to the viral components Early clinical trials Various cancer types [2]
mRNA-carrying oncolytic viruses mRNA loaded into oncolytic viruses for delivery Selective replication in cancer cells and antigen presentation Tumor-specific delivery and amplification of mRNA expression Potential toxicity and systemic spread Immune response to the viral components Preclinical trials Various cancer types [135]
mRNA-nanocomplexes mRNA encapsulated in a nanoparticle for delivery Facilitate cellular uptake and mRNA release Efficient and targeted delivery Potential toxicity and accumulation in liver Immune response to the delivery vehicle Preclinical trials Various cancer types [136]
mRNA-loaded hydrogels mRNA embedded in a hydrogel matrix for delivery Facilitate cellular uptake and mRNA release Sustained release and targeted delivery Lower transfection efficiency than LNPs Inflammation and fibrosis at the injection site Preclinical trials Various cancer types [2]
mRNA-loaded microneedles mRNA coated on microneedles for dermal delivery Facilitate cellular uptake and mRNA release Simple and painless administration Limited to dermal applications Risk of skin irritation and infection Preclinical trials Various cancer types, infectious diseases [137]
mRNA-electrospun fibers mRNA encapsulated in electrospun fibers for delivery Facilitate cellular uptake and mRNA release Sustained release and targeted delivery Limited to topical applications Biocompatibility and toxicity concerns Preclinical trials Various cancer types, infectious diseases [138]
mRNA delivery via ultrasound-targeted microbubble destruction mRNA delivered to the site of interest using ultrasound and microbubbles Increased cellular uptake and gene expression at the site of interest Targeted delivery, non-invasive Limited to superficial tumors, small area of effect Safety of microbubbles Preclinical trials Various cancer types [139]
mRNA delivery via magnetofection mRNA complexed with magnetic particles and delivered using a magnetic field Enhanced cellular uptake and transfection Targeted delivery, non-invasive Limited to superficial tumors, small area of effect Safety of magnetic particles Preclinical trials Various cancer types [140]
mRNA delivery via nanoparticles with tumor-penetrating peptides mRNA encapsulated in nanoparticles functionalized with tumor-penetrating peptides Facilitates the penetration of mRNA-containing nanoparticles into tumor tissue Enhanced tumor-targeting, high transfection efficiency Limited to solid tumors Safety of nanoparticles Preclinical trials Solid tumors [141]
mRNA delivery via bacterial vectors mRNA loaded into attenuated bacteria and delivered to tumor site Amplifies antigen presentation and tumor-specific immune response Enhanced immunogenicity, targeted delivery Potential for bacterial infection and immune response Safety of bacterial vectors Preclinical trials Various cancer types [142]
mRNA delivery via hyaluronan nanogels mRNA encapsulated in hyaluronan-based nanogels and delivered to the site of interest Increased cellular uptake and transfection at the site of interest Targeted delivery, non-toxic Limited to superficial tumors, small area of effect Safety of nanogels Preclinical trials Various cancer types [143]
mRNA delivery via bioresponsive polymeric nanoparticles mRNA encapsulated in polymeric nanoparticles designed to degrade in response to specific stimuli Facilitates site-specific mRNA delivery Targeted delivery, non-toxic Limited to tumors that can be targeted by specific stimuli Safety of nanoparticles Preclinical trials Various cancer types [144]
mRNA delivery via tissue engineering scaffolds mRNA incorporated into tissue engineering scaffolds and delivered to the site of interest Enhanced cellular uptake and transfection at the site of interest Site-specific delivery, potentially long-term antigen expression Limited to solid tumors and tissue-engineered sites Safety of scaffolds Preclinical trials Various cancer types, tissue engineering [145]
mRNA delivery via extracellular vesicles mRNA encapsulated in extracellular vesicles derived from a patient's own cells and delivered to the site of interest Enhanced tumor-targeting, high transfection efficiency Targeted delivery, non-toxic Limited to solid tumors Safety of extracellular vesicles Preclinical trials Solid tumors [146]
mRNA delivery via in vivo electroporation mRNA delivered to tissue via electroporation Facilitates cellular uptake and gene expression Targeted delivery, non-toxic Limited to specific tissue types and requires specialized equipment Risk of tissue damage from electroporation Preclinical trials, some clinical trials Various cancer types [147]
mRNA delivery via dissolvable microneedle arrays mRNA coated onto dissolvable microneedles and applied to skin Facilitates cellular uptake and gene expression in skin Targeted delivery, non-invasive Limited to skin and superficial tumors Safety of microneedles Preclinical trials Skin cancers [148]
mRNA delivery via laser ablation mRNA delivered to tissue via laser ablation Facilitates cellular uptake and gene expression Targeted delivery, non-toxic Limited to specific tissue types and requires specialized equipment Risk of tissue damage from laser ablation Preclinical trials Various cancer types [149]
mRNA delivery via microfluidic chips mRNA delivered to cells via microfluidic chips Facilitates cellular uptake and gene expression Targeted delivery, precise control over flow rates and concentrations Limited to specific cell types and requires specialized equipment Safety of microfluidic chips Preclinical trials Various cancer types [150]
mRNA delivery via electrospray mRNA delivered to tissue via electrospray Facilitates cellular uptake and gene expression Targeted delivery, non-toxic Limited to specific tissue types and requires specialized equipment Safety of electrospray Preclinical trials Various cancer types [151]
mRNA delivery via cell-penetrating peptides mRNA complexed with cell-penetrating peptides and delivered to cells Facilitates cellular uptake and gene expression Targeted delivery, non-toxic Limited to specific cell types Safety of cell-penetrating peptides Preclinical trials Various cancer types [152]
mRNA delivery via gene gun mRNA coated onto gold particles and delivered to tissue via gene gun Facilitates cellular uptake and gene expression Targeted delivery, non-toxic Limited to specific tissue types and requires specialized equipment Risk of tissue damage from gene gun Preclinical trials Various cancer types [153]
mRNA delivery via polymeric carriers mRNA complexed with biodegradable polymeric carriers and delivered to tissue Facilitates cellular uptake and gene expression Targeted delivery, non-toxic, controlled release Limited to specific tissue types and requires specialized equipment Safety of polymeric carriers Preclinical trials Various cancer types [154]
mRNA delivery via lipoplexes mRNA complexed with lipids and delivered to cells Facilitates cellular uptake and gene expression Non-toxic, efficient Limited to specific cell types Safety of lipids Preclinical trials Various cancer types [155]
mRNA delivery via dendrimers mRNA complexed with dendrimers and delivered to cells Facilitates cellular uptake and gene expression Non-toxic, efficient Limited to specific cell types Safety of dendrimers Preclinical trials Various cancer types [156]
mRNA delivery via gold nanoparticles mRNA complexed with gold nanoparticles and delivered to cells Facilitates cellular uptake and gene expression Non-toxic, efficient Limited to specific cell types Safety of gold nanoparticles Preclinical trials Various cancer types [133]
mRNA delivery via viral vectors mRNA loaded into viral vectors and delivered to cells Facilitates cellular uptake and gene expression High transfection efficiency, targeted delivery Risk of immune response and viral integration Safety of viral vectors Preclinical trials Various cancer types [157]
mRNA delivery via cell-based vehicles mRNA loaded into various cell types and delivered to target tissues Facilitates cellular uptake and gene expression Non-toxic, potential for targeting and controlled release Limited to specific cell types and requires specialized equipment Safety of cell-based vehicles Preclinical trials Various cancer types [158]
mRNA delivery via exosomes mRNA encapsulated in exosomes and delivered to target tissues Facilitates cellular uptake and gene expression Non-toxic, potential for targeting and controlled release Limited to specific tissues Safety of exosomes Preclinical trials Various cancer types [159]
mRNA delivery via ribonucleoprotein complexes mRNA complexed with ribonucleoproteins and delivered to cells Facilitates cellular uptake and gene expression Non-toxic, efficient Limited to specific cell types Safety of ribonucleoproteins Preclinical trials Various cancer types [147]
mRNA delivery via inorganic nanoparticles mRNA complexed with inorganic nanoparticles and delivered to cells Facilitates cellular uptake and gene expression Non-toxic, efficient, targeted delivery Limited to specific cell types Safety of inorganic nanoparticles Preclinical trials Various cancer types [147]
mRNA delivery via sonoporation mRNA delivered to tissue via ultrasound-mediated sonoporation Facilitates cellular uptake and gene expression Non-invasive, targeted delivery Limited to specific tissue types and requires specialized equipment Risk of tissue damage from sonoporation Preclinical trials Various cancer types [160]
mRNA delivery via gas-filled microbubbles mRNA delivered to tissue via microbubble-assisted ultrasound Facilitates cellular uptake and gene expression Non-invasive, targeted delivery Limited to specific tissue types and requires specialized equipment Safety of microbubbles Preclinical trials Various cancer types [161]
mRNA delivery via electrical fields mRNA delivered to cells via electrical fields Facilitates cellular uptake and gene expression Non-toxic, efficient Limited to specific cell types and requires specialized equipment Safety of electrical fields Preclinical trials Various cancer types [162]
mRNA delivery via bacterial vectors mRNA loaded into bacterial vectors and delivered to cells Facilitates cellular uptake and gene expression Targeted delivery, high transfection efficiency Risk of immune response and bacterial infection Safety of bacterial vectors Preclinical trials Various cancer types [147]
mRNA delivery via CRISPR-Cas systems mRNA encoding CRISPR-Cas system delivered to cells Facilitates targeted gene editing Precise, efficient Limited to specific cell types and requires specialized equipment Safety of CRISPR-Cas system Preclinical trials Various cancer types [163]
mRNA delivery via cell-penetrating antibodies mRNA complexed with cell-penetrating antibodies and delivered to cells Facilitates cellular uptake and gene expression Non-toxic, potential for targeting and controlled release Limited to specific cell types Safety of cell-penetrating antibodies Preclinical trials Various cancer types [164]
mRNA delivery via non-viral vectors mRNA complexed with non-viral vectors and delivered to cells Facilitates cellular uptake and gene expression Non-toxic, efficient, potential for targeted delivery Limited to specific cell types Safety of non-viral vectors Preclinical trials Various cancer types [165]