“…Also, at the 7th position, guanine nucleotide will be methylated by methyltransferase, which is why the cap is known as a 7-methyl guanylate cap (m7G). Thus, the 5′ cap plays a primary role in producing, regulating mature mRNA, serving as a ribosomal recognition sign, and ensuring mRNA stability during the translation process [ 128 ]. Fig.…”
Section: Transdermal Delivery Of Specific Genetic Materialsmentioning
Gene therapy is a critical constituent of treatment approaches for genetic diseases and has gained tremendous attention. Treating and preventing diseases at the genetic level using genetic materials such as DNA or RNAs could be a new avenue in medicine. However, delivering genes is always a challenge as these molecules are sensitive to various enzymes inside the body, often produce systemic toxicity, and suffer from off-targeting problems. In this regard, transdermal delivery has emerged as an appealing approach to enable a high efficiency and low toxicity of genetic medicines. This review systematically summarizes outstanding transdermal gene delivery methods for applications in skin cancer treatment, vaccination, wound healing, and other therapies.
Graphical abstract
“…Also, at the 7th position, guanine nucleotide will be methylated by methyltransferase, which is why the cap is known as a 7-methyl guanylate cap (m7G). Thus, the 5′ cap plays a primary role in producing, regulating mature mRNA, serving as a ribosomal recognition sign, and ensuring mRNA stability during the translation process [ 128 ]. Fig.…”
Section: Transdermal Delivery Of Specific Genetic Materialsmentioning
Gene therapy is a critical constituent of treatment approaches for genetic diseases and has gained tremendous attention. Treating and preventing diseases at the genetic level using genetic materials such as DNA or RNAs could be a new avenue in medicine. However, delivering genes is always a challenge as these molecules are sensitive to various enzymes inside the body, often produce systemic toxicity, and suffer from off-targeting problems. In this regard, transdermal delivery has emerged as an appealing approach to enable a high efficiency and low toxicity of genetic medicines. This review systematically summarizes outstanding transdermal gene delivery methods for applications in skin cancer treatment, vaccination, wound healing, and other therapies.
Graphical abstract
“…Nucleic acid-based drugs generally enter cells via endocytosis; most of these therapeutics must be formulated as a bioconjugate to facilitate receptor-mediated endocytosis and/or increase their lipophilicity [36][37][38] (Figure 2B). For example, conjugation of an siRNA with anandamide, folate, or cholesterol enables efficient uptake of the siRNA by cells, likely via the corresponding conjugate-specific receptor [39].…”
Section: Bioconjugations Of Asosmentioning
confidence: 99%
“…Oligonucleotide bioconjugates offer the potential for enhanced drug delivery, but recent advances in nanotechnology have further benefited the transport of therapeutic ASOs across biological barriers and improved their pharmacokinetics in circulating blood. Several nanoparticle-mediated delivery systems have been developed [15,18,[36][37][38] (Figure 2C).…”
Section: Vehicle-mediated Delivery Of Asosmentioning
Nucleic acid-based therapeutics have demonstrated their efficacy in the treatment of various diseases and vaccine development. Antisense oligonucleotide (ASO) technology exploits a single-strand short oligonucleotide to either cause target RNA degradation or sterically block the binding of cellular factors or machineries to the target RNA. Chemical modification or bioconjugation of ASOs can enhance both its pharmacokinetic and pharmacodynamic performance, and it enables customization for a specific clinical purpose. ASO-based therapies have been used for treatment of genetic disorders, cancer and viral infections. In particular, ASOs can be rapidly developed for newly emerging virus and their reemerging variants. This review discusses ASO modifications and delivery options as well as the design of antiviral ASOs. A better understanding of the viral life cycle and virus-host interactions as well as advances in oligonucleotide technology will benefit the development of ASO-based antiviral therapies.
“…They are subjected to significant limitations concerning immunogenicity and toxicity [ 120 ]. Although a lot of efforts have been made in order to eliminate these challenges, e.g., by using mutant vectors, self-inactivating vectors, nonsegmented negative-stranded (NSNS) viruses, such as Sendai virus (SeV) [ 119 , 121 , 122 ], the superiority of non-viral vectors for mRNA delivery is still integral [ 12 , 123 ].…”
In the quest for a formidable weapon against the SARS-CoV-2 pandemic, mRNA therapeutics have stolen the spotlight. mRNA vaccines are a prime example of the benefits of mRNA approaches towards a broad array of clinical entities and druggable targets. Amongst these benefits is the rapid cycle “from design to production” of an mRNA product compared to their peptide counterparts, the mutability of the production line should another target be chosen, the side-stepping of safety issues posed by DNA therapeutics being permanently integrated into the transfected cell’s genome and the controlled precision over the translated peptides. Furthermore, mRNA applications are versatile: apart from vaccines it can be used as a replacement therapy, even to create chimeric antigen receptor T-cells or reprogram somatic cells. Still, the sudden global demand for mRNA has highlighted the shortcomings in its industrial production as well as its formulation, efficacy and applicability. Continuous, smart mRNA manufacturing 4.0 technologies have been recently proposed to address such challenges. In this work, we examine the lab and upscaled production of mRNA therapeutics, the mRNA modifications proposed that increase its efficacy and lower its immunogenicity, the vectors available for delivery and the stability considerations concerning long-term storage.
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