Muscle-Specific Promoters for Gene Therapy
| Dublin Core | PKP Metadata Items | Metadata for this Document | |
| 1. | Title | Title of document | Muscle-Specific Promoters for Gene Therapy |
| 2. | Creator | Author's name, affiliation, country | Victoria V. Skopenkova; Institute of Gene Biology, Russian Academy of Sciences; Marlin Biotech LLC; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences; Россия |
| 2. | Creator | Author's name, affiliation, country | Tatiana V. Egorova; Institute of Gene Biology, Russian Academy of Sciences; Marlin Biotech LLC; Россия |
| 2. | Creator | Author's name, affiliation, country | Maryana V. Bardina; Institute of Gene Biology, Russian Academy of Sciences; Marlin Biotech LLC; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences; Россия |
| 3. | Subject | Discipline(s) | |
| 3. | Subject | Keyword(s) | Gene therapy; muscle-specific promoters; AAV; natural promoters; synthetic promoters |
| 4. | Description | Abstract | Many genetic diseases that are responsible for muscular disorders have been described to date. Gene replacement therapy is a state-of-the-art strategy used to treat such diseases. In this approach, the functional copy of a gene is delivered to the affected tissues using viral vectors. There is an urgent need for the design of short, regulatory sequences that would drive a high and robust expression of a therapeutic transgene in skeletal muscles, the diaphragm, and the heart, while exhibiting limited activity in non-target tissues. This review focuses on the development and improvement of muscle-specific promoters based on skeletal muscle α-actin, muscle creatine kinase, and desmin genes, as well as other genes expressed in muscles. The current approaches used to engineer synthetic muscle-specific promoters are described. Other elements of the viral vectors that contribute to tissue-specific expression are also discussed. A special feature of this review is the presence of up-to-date information on the clinical and preclinical trials of gene therapy drug candidates that utilize muscle-specific promoters. |
| 5. | Publisher | Organizing agency, location | Acta Naturae Ltd |
| 6. | Contributor | Sponsor(s) | |
| 7. | Date | (DD-MM-YYYY) | 15.03.2021 |
| 8. | Type | Status & genre | Peer-reviewed Article |
| 8. | Type | Type | Review Article |
| 9. | Format | File format | |
| 10. | Identifier | Uniform Resource Identifier | https://actanaturae.ru/2075-8251/article/view/11063 |
| 10. | Identifier | Digital Object Identifier (DOI) | 10.32607/actanaturae.11063 |
| 11. | Source | Title; vol., no. (year) | Acta Naturae; Vol 13, No 1 (2021) |
| 12. | Language | English=en | ru |
| 13. | Relation | Supp. Files |
Fig. 1. The structure of a eukaryotic promoter. The eukaryotic promoter consists of the core promoter, the proximal promoter elements, and distal regulatory elements. In the core promoter conserved motifs are shown with consensus sequences and the position from the transcription start site (190KB) doi: 10.32607/20758251-2021-13-1-47-58-2173 Fig. 2. Promoters based on the ACTA1/HSA gene. (A) – the full-length HSA promoter includes the distal region, the proximal region (PR), and the basal region, which consists of the noncoding exon (+1...+90) and the first intron fragment (+91...+239); (B) – shortened version of the HSA promoter; (C) – the chimeric HSA/CMV promoter consisting of a fragment of the HSA promoter and the CMV promoter (100KB) doi: 10.32607/20758251-2021-13-1-47-58-2174 Fig. 3. Mck-based promoters. All the constructs contain the MCK enhancer and the MCK promoter, with different modifications (153KB) doi: 10.32607/20758251-2021-13-1-47-58-2175 Fig. 4. Promoters based on the human DES gene. Promoter (A) includes the locus control region of the desmin gene (18.7 kbp) with introduced deletions, the enhancer, the silencer, and the proximal promoter (PP). Promoter (B) contains a deletion in the silencer and the TATA box added to the core promoter. Promoters (C) and (D) have deletions in the distal regions (97KB) doi: 10.32607/20758251-2021-13-1-47-58-2176 Fig. 5. Synthetic promoters. The SPc5-12 promoter consists of a combination of four muscle-specific TFBSs (TEF1, SRE, MEF1, and MEF2) and the core promoter (a fragment of the promoter of the chicken skeletal muscle α-actin gene). The SP-301 promoter is a combination of muscle-specific TFBSs, viral elements, and conserved cis-regulatory elements ligated in forward and reverse orientation. The MH promoter consists of the human desmin gene enhancer linked to the enhancer, the core promoter, and the first intron of the mouse Ckm gene. Sk-CRM4/Des is the regulatory module Sk-CRM4 ligated to the desmin promoter and the MVM intron (345KB) doi: 10.32607/20758251-2021-13-1-47-58-2177 Fig. 6. Typical elements of the AVV expression cassette. Orange blocks (the promoter, the transgene, and polyadenylation signal (pA)) are the basic components of the cassette. Accessory cis-regulatory elements, such as intron (I), WPRE, and the microRNA binding sites (3’-UTR), can also be inserted to enhance expression efficiency. The cassette is flanked by inverted terminal repeats (ITR) (177KB) doi: 10.32607/20758251-2021-13-1-47-58-2178 |
| 14. | Coverage | Geo-spatial location, chronological period, research sample (gender, age, etc.) | |
| 15. | Rights | Copyright and permissions |
Copyright (c) 2021 Skopenkova V.V., Egorova T.V., Bardina M.V. This work is licensed under a Creative Commons Attribution 4.0 International License. |