Nucleic acid vaccines have attracted enormous attention for resolving the limitations of conventional vaccines using live attenuated viruses. Because nucleic acid vaccines can be produced rapidly in response to the em...Nucleic acid vaccines have attracted enormous attention for resolving the limitations of conventional vaccines using live attenuated viruses. Because nucleic acid vaccines can be produced rapidly in response to the emergence of new virus strains, they are more appropriate for the control of urgent epidemic and pandemic issues. In particular, messenger RNA （mRNA） vaccines have evolved as a new type of nucleic acid vaccines in accordance with their superior protein expression and a lack of mutagenesis as compared with DNA vaccines. Using mRNA vaccines, large amounts of target proteins can be expressed in immune cells for efficient immunization. For instance, antigen-specific vaccination is a feasible option involving the expression of specific antigens in antigen-presenting cells. Immunological reactions are modulated by expressing several proteins associated with stimulation or maturation of immune cells. In addition, mRNA vaccines can stimulate innate immunity through specific recognition by pattern recognition receptors. On the basis of these remarkable properties, mRNA vaccines have been used for prophylactic and therapeutic applications. This review highlights the role of mRNA vaccines as prophylactic vaccines for prevention of future infections and as therapeutic vaccines for cancer immunotherapy. In addition to the conventional type of mRNA vaccines, RNA replicons （self-amplifying mRNA vaccines） will be described.展开更多
Successful development of a new drug is prohibitively expensive, and is estimated to cost approxi- mately S100-500 million US dollars for a single clinical drug. Yet, a newly developed drug can only enjoy its patent p...Successful development of a new drug is prohibitively expensive, and is estimated to cost approxi- mately S100-500 million US dollars for a single clinical drug. Yet, a newly developed drug can only enjoy its patent protection for 18 years, meaning that after this protected time period, any company can manufacture this product and thus the profit generated by this drug entity would reduce dramatically. Most critically, once a drug is being synthesized, its physical, chemical, and biological attri- butes such as bioavailability and in vivo pharmacokinetics are all completely fixed and cannot be changed. In principal and practice, only the application of an appro- priately designed drug delivery system （DDS） is able to overcome such limitations, and yet the cost of developing a novel drug delivery system is less than 10% of that of developing a new drug. Because of these reasons, the new trend in pharmaceutical development has already begun to shift from the single direction of developing new drugs in the past to a combined mode of developing both new drugs and innovative drug delivery systems in this century. Hence, for developing countries with relatively limited financial resources, a smart strategic move would be to focus on the development of new DDS, which has a significantly higher benefit/risk ratio when comparing to the development of a new drug. Because of the unmatched reaction efficiency and a repetitive action mode, the therapeutic activity of a single bio-macromolecular drug （e.g., protein toxins, gene products, etc.） is equivalent to about 10^6- 10^8 of that from a conventional small molecule anti-cancer agent （e.g., doxorubicin）. Hence, bio-macromolecular drugs have been recognized around the world as the future ＂drug-of-choice＂. Yet, among the 〉 10000 drugs that are currently available, only -150 of them belong to these bio- macromolecular drugs （an exceedingly low 1.2%）, reflect- ing the difficulties of utilizing these agents in clinical practice. In general, the bottleneck limitations of these bio- macromolecular drugs are two-fold： （1） the absence of a preferential action of the drug on tumor cells as opposed to normal tissues, and （2） the lack of ability to cross the tumor cell membrane. In this review, we provide strategies of how to solve these problems simultaneously and collec- tively via the development of innovative drug delivery systems. Since worldwide progress on bio-macromolecular therapeutics still remains in the infant stage and thus open for an equal-ground competition, we wish that this review would echo the desire to industrialized countries such as China to set up its strategic plan on developing delivery systems for these bio-macromolecular drugs, thereby realizing their clinical potential.展开更多
文摘Nucleic acid vaccines have attracted enormous attention for resolving the limitations of conventional vaccines using live attenuated viruses. Because nucleic acid vaccines can be produced rapidly in response to the emergence of new virus strains, they are more appropriate for the control of urgent epidemic and pandemic issues. In particular, messenger RNA （mRNA） vaccines have evolved as a new type of nucleic acid vaccines in accordance with their superior protein expression and a lack of mutagenesis as compared with DNA vaccines. Using mRNA vaccines, large amounts of target proteins can be expressed in immune cells for efficient immunization. For instance, antigen-specific vaccination is a feasible option involving the expression of specific antigens in antigen-presenting cells. Immunological reactions are modulated by expressing several proteins associated with stimulation or maturation of immune cells. In addition, mRNA vaccines can stimulate innate immunity through specific recognition by pattern recognition receptors. On the basis of these remarkable properties, mRNA vaccines have been used for prophylactic and therapeutic applications. This review highlights the role of mRNA vaccines as prophylactic vaccines for prevention of future infections and as therapeutic vaccines for cancer immunotherapy. In addition to the conventional type of mRNA vaccines, RNA replicons （self-amplifying mRNA vaccines） will be described.
文摘Successful development of a new drug is prohibitively expensive, and is estimated to cost approxi- mately S100-500 million US dollars for a single clinical drug. Yet, a newly developed drug can only enjoy its patent protection for 18 years, meaning that after this protected time period, any company can manufacture this product and thus the profit generated by this drug entity would reduce dramatically. Most critically, once a drug is being synthesized, its physical, chemical, and biological attri- butes such as bioavailability and in vivo pharmacokinetics are all completely fixed and cannot be changed. In principal and practice, only the application of an appro- priately designed drug delivery system （DDS） is able to overcome such limitations, and yet the cost of developing a novel drug delivery system is less than 10% of that of developing a new drug. Because of these reasons, the new trend in pharmaceutical development has already begun to shift from the single direction of developing new drugs in the past to a combined mode of developing both new drugs and innovative drug delivery systems in this century. Hence, for developing countries with relatively limited financial resources, a smart strategic move would be to focus on the development of new DDS, which has a significantly higher benefit/risk ratio when comparing to the development of a new drug. Because of the unmatched reaction efficiency and a repetitive action mode, the therapeutic activity of a single bio-macromolecular drug （e.g., protein toxins, gene products, etc.） is equivalent to about 10^6- 10^8 of that from a conventional small molecule anti-cancer agent （e.g., doxorubicin）. Hence, bio-macromolecular drugs have been recognized around the world as the future ＂drug-of-choice＂. Yet, among the 〉 10000 drugs that are currently available, only -150 of them belong to these bio- macromolecular drugs （an exceedingly low 1.2%）, reflect- ing the difficulties of utilizing these agents in clinical practice. In general, the bottleneck limitations of these bio- macromolecular drugs are two-fold： （1） the absence of a preferential action of the drug on tumor cells as opposed to normal tissues, and （2） the lack of ability to cross the tumor cell membrane. In this review, we provide strategies of how to solve these problems simultaneously and collec- tively via the development of innovative drug delivery systems. Since worldwide progress on bio-macromolecular therapeutics still remains in the infant stage and thus open for an equal-ground competition, we wish that this review would echo the desire to industrialized countries such as China to set up its strategic plan on developing delivery systems for these bio-macromolecular drugs, thereby realizing their clinical potential.
