mRNA-based therapeutics represent a new class of drugs that deliver genetic information to cells, enabling the transient expression of proteins. This review discusses the current state of mRNA-based drug technologies and their applications, highlighting key challenges and opportunities in developing these into a new class of drugs. mRNA-based cancer immunotherapies and infectious disease vaccines have entered clinical development, while emerging approaches include in vivo delivery of IVT mRNA to replace or supplement proteins, generation of pluripotent stem cells, and genome engineering using IVT mRNA-encoded designer nucleases. IVT mRNA does not need to enter the nucleus to be functional; once in the cytoplasm, it is translated instantly. Unlike DNA therapeutics, IVT mRNA does not integrate into the genome, thus avoiding insertional mutagenesis. The production of IVT mRNA is relatively simple and inexpensive, leading to broad interest in its development. In therapeutic cancer vaccination, IVT mRNA has undergone extensive preclinical investigation and reached Phase III clinical testing. In other areas, such as protein-replacement therapies, the development of IVT mRNA-based therapeutics is at the preclinical stage. The primary compartment of pharmacodynamic activity of IVT mRNA is the cytoplasm. IVT mRNA must enter the cytoplasm from the extracellular space, and its cytoplasmic bioavailability is determined by factors such as rapid degradation by RNases and cell membrane barriers. The translation and stability of IVT mRNA are critical for its pharmacokinetics. The protein product translated from IVT mRNA undergoes post-translational modification and is the bioactive compound. The half-lives of both the IVT mRNA template and the protein product are critical determinants of the pharmacokinetics of mRNA-based therapeutics. Efforts have been made to improve the translation and stability of IVT mRNA by modifying structural elements such as the 5' cap, 5'- and 3'-UTRs, the coding region, and the poly(A) tail. These modifications enhance the production of significant levels of the encoded protein over a longer timeframe. The 5' cap is crucial for efficient translation, and modifications such as anti-reverse cap analogues have been introduced to improve translational efficiency. The poly(A) tail regulates the stability and translational efficiency of mRNA in synergy with the 5' cap, internal ribosomal entry site, and other determinants. The length of the poly(A) tail affects stability, with optimal lengths between 120 and 150 nucleotides. Codon optimization improves translational efficiency by replacing rare codons with synonymous frequent codons. However, some proteins require slow translation for proper folding, and codon optimization should eliminate sources of antigenic peptides. The immune-stimulatory activity of IVT mRNA is beneficial for vaccination, leading to potent antigen-specific immune responses. However, in protein-replacement therapies, activation of the innate immune system is a major disadvantage. Recent progress in identifying RNA sensors andmRNA-based therapeutics represent a new class of drugs that deliver genetic information to cells, enabling the transient expression of proteins. This review discusses the current state of mRNA-based drug technologies and their applications, highlighting key challenges and opportunities in developing these into a new class of drugs. mRNA-based cancer immunotherapies and infectious disease vaccines have entered clinical development, while emerging approaches include in vivo delivery of IVT mRNA to replace or supplement proteins, generation of pluripotent stem cells, and genome engineering using IVT mRNA-encoded designer nucleases. IVT mRNA does not need to enter the nucleus to be functional; once in the cytoplasm, it is translated instantly. Unlike DNA therapeutics, IVT mRNA does not integrate into the genome, thus avoiding insertional mutagenesis. The production of IVT mRNA is relatively simple and inexpensive, leading to broad interest in its development. In therapeutic cancer vaccination, IVT mRNA has undergone extensive preclinical investigation and reached Phase III clinical testing. In other areas, such as protein-replacement therapies, the development of IVT mRNA-based therapeutics is at the preclinical stage. The primary compartment of pharmacodynamic activity of IVT mRNA is the cytoplasm. IVT mRNA must enter the cytoplasm from the extracellular space, and its cytoplasmic bioavailability is determined by factors such as rapid degradation by RNases and cell membrane barriers. The translation and stability of IVT mRNA are critical for its pharmacokinetics. The protein product translated from IVT mRNA undergoes post-translational modification and is the bioactive compound. The half-lives of both the IVT mRNA template and the protein product are critical determinants of the pharmacokinetics of mRNA-based therapeutics. Efforts have been made to improve the translation and stability of IVT mRNA by modifying structural elements such as the 5' cap, 5'- and 3'-UTRs, the coding region, and the poly(A) tail. These modifications enhance the production of significant levels of the encoded protein over a longer timeframe. The 5' cap is crucial for efficient translation, and modifications such as anti-reverse cap analogues have been introduced to improve translational efficiency. The poly(A) tail regulates the stability and translational efficiency of mRNA in synergy with the 5' cap, internal ribosomal entry site, and other determinants. The length of the poly(A) tail affects stability, with optimal lengths between 120 and 150 nucleotides. Codon optimization improves translational efficiency by replacing rare codons with synonymous frequent codons. However, some proteins require slow translation for proper folding, and codon optimization should eliminate sources of antigenic peptides. The immune-stimulatory activity of IVT mRNA is beneficial for vaccination, leading to potent antigen-specific immune responses. However, in protein-replacement therapies, activation of the innate immune system is a major disadvantage. Recent progress in identifying RNA sensors and