Modified mRNA as an alternative to plasmid DNA (pDNA) for transcript replacement and vaccination therapy

Abstract

Introduction: Current gene therapy involves replacement of defective gene by delivery of healthy genetic material to precede normal function. Virus-mediated gene delivery is the most successful and efficient method for gene therapy, but it has been challenged due to serious safety concerns. Conversely, gene delivery using plasmid DNA (pDNA) is considered safer, but its transfection efficiency is much lower than virus-mediated gene transfer. Recently, mRNA has been suggested as an alternative option to avoid undesired insertion of delivered DNA sequences with higher transfection efficiency and stability. Area covered: In this review, we summarize the currently available strategies of mRNA modification to increase the therapeutic efficacy; we also highlight the recent improvements of mRNA delivery for in vivo applications of gene therapy. Expert opinion: The use of mRNA-based gene transfer could indeed be a promising new strategy for gene therapy. Notable advantages include no risk of integration into the genomic DNA, adjustable gene expression and easier modulation of the immune system. By reducing or utilizing the immunogenic properties, mRNA offers a promising tool for gene/or transcript replacement.

Folate-Targeted mRNA Delivery Using Chitosan-Functionalized Selenium Nanoparticles: Potential in Cancer Immunotherapy

“…Another strategy for cancer immunotherapy lies in utilizing genetically modified immune cells, viz. T and dendritic cells to respond to tumour antigens [10]. The numerous mutations in the coding exons of cancer cells are potential targets for antigens, with studies reporting the delivery of mRNA encoding tumour-associated antigens to dendritic and tumor cells [11,12].…”

“…Safe and efficient delivery of a nucleic acid to a target site of action remains a major obstacle to successful gene therapy, halting many clinical trials [13]. The success of therapeutic mRNA delivery has been further hindered by mRNA instability, inefficient delivery and uptake, and limited transfection [10]. Core-shell nanoparticles composed of inorganic and organic materials are efficient delivery vehicles due to their defined physical features, tunable size, and versatile chemical and physical properties, which can be used over a wide range of gene and drug delivery platforms [14][15][16][17], in addition to their multifunctional capabilities, enhanced biocompatibility, and synergistic properties.…”

Development of a Novel Polymer-Based mRNA Coating for Surgical Suture to Enhance Wound Healing

“…However, several known disadvantages exist when it comes to DNA-based gene therapy such as the approaching potential mutagenic effect through false integration into the host's genome [41,42]. But this threat does not exist when pursuing a mRNA-based gene therapy approach where the nucleic acid does not enter the nucleus and furthermore the administration of therapeutic mRNA is only temporary and will end when the suture is removed.…”

DNA and RNA Vaccines: Current Status, Quality Requirements and Specific Aspects of Preclinical Studies

“…Первый основан на использовании ферментов вируса коровьей оспы, один из которых добавляет m7GpppN, а второй -2-О-метильную группу к предпоследнему нуклеотиду, в результате формируется 5′-кэп, идентичный по структуре эукариотическим мРНК. Второй, наиболее часто используемый подход, заключается во включении синтетических аналогов (например, антиреверсные ARCAs или m 2 7,3′-O GpppG) при транскрипции in vitro [24][25][26][27]. Добавление UTR, содержащих различные регуляторные элементы, используется для повышения эффективности трансляции и повышения стабильности мРНК.…”