Understanding In Vivo Fate of Nucleic Acid and Gene Medicines for the Rational Design of Drugs
Nucleic acid and genetic medicines are increasingly being developed, owing to their potential to treat a variety of intractable diseases. A comprehensive understanding of the in vivo fate of these agents is vital for the rational design, discovery, and fast and straightforward development of the dru...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/2/159 |
| _version_ | 1797407396309499904 |
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| author | Shintaro Fumoto Tsuyoshi Yamamoto Kazuya Okami Yuina Maemura Chisato Terada Asako Yamayoshi Koyo Nishida |
| author_facet | Shintaro Fumoto Tsuyoshi Yamamoto Kazuya Okami Yuina Maemura Chisato Terada Asako Yamayoshi Koyo Nishida |
| author_sort | Shintaro Fumoto |
| collection | DOAJ |
| description | Nucleic acid and genetic medicines are increasingly being developed, owing to their potential to treat a variety of intractable diseases. A comprehensive understanding of the in vivo fate of these agents is vital for the rational design, discovery, and fast and straightforward development of the drugs. In case of intravascular administration of nucleic acids and genetic medicines, interaction with blood components, especially plasma proteins, is unavoidable. However, on the flip side, such interaction can be utilized wisely to manipulate the pharmacokinetics of the agents. In other words, plasma protein binding can help in suppressing the elimination of nucleic acids from the blood stream and deliver naked oligonucleotides and gene carriers into target cells. To control the distribution of these agents in the body, the ligand conjugation method is widely applied. It is also important to understand intracellular localization. In this context, endocytosis pathway, endosomal escape, and nuclear transport should be considered and discussed. Encapsulated nucleic acids and genes must be dissociated from the carriers to exert their activity. In this review, we summarize the in vivo fate of nucleic acid and gene medicines and provide guidelines for the rational design of drugs. |
| first_indexed | 2024-03-09T03:40:49Z |
| format | Article |
| id | doaj.art-d07e2f37dcf949f0bd0180eca5413597 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T03:40:49Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-d07e2f37dcf949f0bd0180eca54135972023-12-03T14:41:44ZengMDPI AGPharmaceutics1999-49232021-01-0113215910.3390/pharmaceutics13020159Understanding In Vivo Fate of Nucleic Acid and Gene Medicines for the Rational Design of DrugsShintaro Fumoto0Tsuyoshi Yamamoto1Kazuya Okami2Yuina Maemura3Chisato Terada4Asako Yamayoshi5Koyo Nishida6Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, JapanGraduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, JapanGraduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, JapanGraduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, JapanGraduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, JapanGraduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, JapanGraduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, JapanNucleic acid and genetic medicines are increasingly being developed, owing to their potential to treat a variety of intractable diseases. A comprehensive understanding of the in vivo fate of these agents is vital for the rational design, discovery, and fast and straightforward development of the drugs. In case of intravascular administration of nucleic acids and genetic medicines, interaction with blood components, especially plasma proteins, is unavoidable. However, on the flip side, such interaction can be utilized wisely to manipulate the pharmacokinetics of the agents. In other words, plasma protein binding can help in suppressing the elimination of nucleic acids from the blood stream and deliver naked oligonucleotides and gene carriers into target cells. To control the distribution of these agents in the body, the ligand conjugation method is widely applied. It is also important to understand intracellular localization. In this context, endocytosis pathway, endosomal escape, and nuclear transport should be considered and discussed. Encapsulated nucleic acids and genes must be dissociated from the carriers to exert their activity. In this review, we summarize the in vivo fate of nucleic acid and gene medicines and provide guidelines for the rational design of drugs.https://www.mdpi.com/1999-4923/13/2/159liposomelipid nanoparticleplasmid DNAoligonucleotidetransfectionmechanism |
| spellingShingle | Shintaro Fumoto Tsuyoshi Yamamoto Kazuya Okami Yuina Maemura Chisato Terada Asako Yamayoshi Koyo Nishida Understanding In Vivo Fate of Nucleic Acid and Gene Medicines for the Rational Design of Drugs Pharmaceutics liposome lipid nanoparticle plasmid DNA oligonucleotide transfection mechanism |
| title | Understanding In Vivo Fate of Nucleic Acid and Gene Medicines for the Rational Design of Drugs |
| title_full | Understanding In Vivo Fate of Nucleic Acid and Gene Medicines for the Rational Design of Drugs |
| title_fullStr | Understanding In Vivo Fate of Nucleic Acid and Gene Medicines for the Rational Design of Drugs |
| title_full_unstemmed | Understanding In Vivo Fate of Nucleic Acid and Gene Medicines for the Rational Design of Drugs |
| title_short | Understanding In Vivo Fate of Nucleic Acid and Gene Medicines for the Rational Design of Drugs |
| title_sort | understanding in vivo fate of nucleic acid and gene medicines for the rational design of drugs |
| topic | liposome lipid nanoparticle plasmid DNA oligonucleotide transfection mechanism |
| url | https://www.mdpi.com/1999-4923/13/2/159 |
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