Production and Application of Multicistronic Constructs for Various Human Disease Therapies
Abstract
:1. Introduction
2. IRES
3. Self-Cleaving 2A Peptides
4. Multicistronic Vectors for Neurodegenerative Disease Therapy
5. Multicistronic Vectors for Metabolic Disease Therapy
6. Multicistronic Vectors for the Treatment of Autoimmune Diseases
7. Multicistronic Vectors for Cardiovascular Disease Therapy
8. Multicistronic Vectors for Cancer Therapy
9. Multicistronic Vectors for the Prevention of Viral and Bacterial Infections
10. Conclusions and Future Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Characteristic | Properties of Protein Synthesis | Size | Gene Expression Level | Cleavage |
---|---|---|---|---|
IRES | Ribosome dissociates when the synthesis of the first gene is complete, the synthesis is interrupted, a new translation initiation complex is assembled in the IRES region | Large (over 500 bp) | The translation efficiency of the gene located downstream of the IRES is much lower than that of the gene located upstream of the IRES | The resulting proteins are always separated from each other |
2A peptides | Continuous synthesis of two proteins. Ribosomal skipping occurs after the synthesis of the first gene is complete, synthesis continues without the dissociation of ribosome | Small (54–66 bp) | Better correlation of the expression of genes placed upstream and downstream of the peptide sequence | Incomplete digestion of protein products is possible |
Multiple promoters | Two separate transcription units, completely separated synthesis | Large | Poor correlation of the expression of two genes | Independent products |
Splicing signals | Two separate transcription units, completely separated synthesis | Small | Uncertain correlation of the expression of two genes | Independent products |
Fusion of genes | One chimeric polypeptide is translated, which can lead to impaired function | No intermediate sequences | Guaranteed co-expression | Not cleaved product |
Cleavage factors | Two proteins are translated together | Small | Guaranteed co-expression | Cleaved by cellular proteases after protein synthesis |
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Shaimardanova, A.A.; Chulpanova, D.S.; Kitaeva, K.V.; Abdrakhmanova, I.I.; Chernov, V.M.; Rutland, C.S.; Rizvanov, A.A.; Solovyeva, V.V. Production and Application of Multicistronic Constructs for Various Human Disease Therapies. Pharmaceutics 2019, 11, 580. https://doi.org/10.3390/pharmaceutics11110580
Shaimardanova AA, Chulpanova DS, Kitaeva KV, Abdrakhmanova II, Chernov VM, Rutland CS, Rizvanov AA, Solovyeva VV. Production and Application of Multicistronic Constructs for Various Human Disease Therapies. Pharmaceutics. 2019; 11(11):580. https://doi.org/10.3390/pharmaceutics11110580
Chicago/Turabian StyleShaimardanova, Alisa A., Daria S. Chulpanova, Kristina V. Kitaeva, Ilmira I. Abdrakhmanova, Vladislav M. Chernov, Catrin S. Rutland, Albert A. Rizvanov, and Valeriya V. Solovyeva. 2019. "Production and Application of Multicistronic Constructs for Various Human Disease Therapies" Pharmaceutics 11, no. 11: 580. https://doi.org/10.3390/pharmaceutics11110580