AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Genes & Diseases Article
PDF (3 MB)
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Full Length Article | Open Access

Prolonged control of insulin-dependent diabetes via intramuscular expression of plasmid-encoded single-strand insulin analogue

Lu Denga,1, Ping Yanga,1, Caixia Lib( ), Lifang Xiea, Wanling Lua, Yanhan Zhanga, Ming Liuc, Gang Wanga( )
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610064, China
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, Sichuan 610041, China
Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan 610044, China

Peer review under responsibility of Chongqing Medical University.

1 These authors contributed equally to this work.

Show Author Information

Abstract

Daily insulin injection is necessary for the treatment of the insulin-dependent diabetes. However, the process is painful and inconvenient. Accordingly, we have made exploratory efforts to establish an alternative method for continuous insulin supply via intramuscular injection of a designed plasmid encoding the single-strand insulin analogue (SIA), which provides safe, effective and prolonged control of insulin-dependent diabetes. To generate a SIA, a short flexible peptide was alternatively introduced into the natural proinsulin to replace its original long and rigid C-peptide. Then, the synthetic promoter SP301 was used to drive potent and specific expression of SIA in skeletal muscle cells. By combining the Pluronic L64 and low-voltage electropulse (L/E), the specialized gene delivery technique was applied to efficiently transfer the constructed plasmid into skeletal muscle cells via intramuscular injection. Through these efforts, a plasmid-based intramuscular gene expression system was established and improved, making it applicable for gene therapy. The plasmid-expressed SIA showed biological functions that were similar to that of natural insulin. A single L/E-pSP301-SIA administration provided sustained SIA expression in vivo for about 1.5 months. In addition, the diabetic mice treated with L/E-pSP301-SIA were much healthier than those with other treatments. This plasmid-based system was safe for the treatment of diabetes and did not cause immune responses or pathological damage. The results confirmed that, in a mouse model, long-term positive effects were achieved by a single intramuscular L/E-pSP301-SIA injection, which consequently provided reliable experimental basis for its clinical application for the treatment of diabetes mellitus with promising prospects.

Keywords

Gene therapyDiabetesPlasmidIntramuscular injectionSingle-strand insulin analogue (SIA)Synthetic promoter

References

1

Yao D, GangYi Y, QiNan W. Autophagic dysfunction of β cell dysfunction in type 2 diabetes, a double-edged sword. Genes Dis. 2020;8(4):438–447.
Crossref Google Scholar
2

Tanabe M, Motonaga R, Terawaki Y, et al. Prescription of oral hypoglycemic agents for patients with type 2 diabetes mellitus: a retrospective cohort study using a Japanese hospital database. J Diabetes Investig. 2017;8(2):227–234.
Crossref Google Scholar
3

Crunkhorn S. Gene therapy: reprogramming α-cells reverses diabetes. Nat Rev Drug Discov. 2018;17(2):93.
Crossref Google Scholar
4

Pathak V, Pathak NM, O’Neill CL, et al. Therapies for type 1 diabetes: current scenario and future perspectives. Clin Med Insights Endocrinol Diabetes. 2019;12:1179551419844521.
Crossref Google Scholar
5

Lebreton F, Lavallard V, Bellofatto K, et al. Insulin-producing organoids engineered from islet and amniotic epithelial cells to treat diabetes. Nat Commun. 2019;10(1):4491.
Crossref Google Scholar
6

Qiu YH, Deng FY, Li MJ, et al. Identification of novel risk genes associated with type 1 diabetes mellitus using a genome-wide gene-based association analysis. J Diabetes Investig. 2014;5(6):649–656.
Crossref Google Scholar
7

Bhattacharya S, Bank S, Maiti S, et al. The control of hyperglycemia by estriol and progesterone in alloxan induced type Ⅰ diabetes mellitus mice model through hepatic insulin synthesis. Int J Biomed Sci. 2014;10(1):8–15.
Crossref Google Scholar
8

Every AL, Kramer DR, Mannering SI, et al. Intranasal vaccination with proinsulin DNA induces regulatory CD4+ T cells that prevent experimental autoimmune diabetes. J Immunol. 2006;176(8):4608–4615.
Crossref Google Scholar
9

Yoon JW, Jun HS. Recent advances in insulin gene therapy for type 1 diabetes. Trends Mol Med. 2002;8(2):62–68.
Crossref Google Scholar
10

Handorf AM, Sollinger HW, Alam T. Insulin gene therapy for type 1 diabetes mellitus. Exp Clin Transplant. 2015;13(Suppl 1):37–45.
Google Scholar
11

Chen YH, Keiser MS, Davidson BL. Viral vectors for gene transfer. Curr Protoc Mol Biol. 2018;8(4):e58.
Crossref Google Scholar
12

Flotte TR, Solow R, Owens RA, et al. Gene expression from adeno-associated virus vectors in airway epithelial cells. Am J Respir Cell Mol Biol. 1992;7(3):349–356.
Crossref Google Scholar
13

Nguyen GN, Everett JK, Kafle S, et al. A long-term study of AAV gene therapy in dogs with hemophilia A identifies clonal expansions of transduced liver cells. Nat Biotechnol. 2021;39 (1):47–55.
Crossref Google Scholar
14

Liu Y, He Y, Wang Y, et al. Synthetic promoter for efficient and muscle-specific expression of exogenous genes. Plasmid. 2019;106:102441.
Crossref Google Scholar
15

Liu S, Ma L, Tan R, et al. Safe and efficient local gene delivery into skeletal muscle via a combination of Pluronic L64 and modified electrotransfer. Gene Ther. 2014;21(6):558–565.
Crossref Google Scholar
16

Chen J, Luo J, Zhao Y, et al. Increase in transgene expression by pluronic L64-mediated endosomal/lysosomal escape through its membrane-disturbing action. ACS Appl Mater Interfaces. 2015;7(13):7282–7293.
Crossref Google Scholar
17

Song H, Liu S, Li C, et al. Pluronic L64-mediated stable HIF-1α expression in muscle for therapeutic angiogenesis in mouse hindlimb ischemia. Int J Nanomed. 2014;9:3439–3452.
Crossref Google Scholar
18

Chaudhry ZZ, Morris DL, Moss DR, et al. Streptozotocin is equally diabetogenic whether administered to fed or fasted mice. Lab Anim. 2013;47(4):257–265.
Crossref Google Scholar
19

Deeds MC, Anderson JM, Armstrong AS, et al. Single dose streptozotocin-induced diabetes: considerations for study design in islet transplantation models. Lab Anim. 2011;45(3):131–140.
Crossref Google Scholar
20

Tevz G, Pavlin D, Kamensek U, et al. Gene electrotransfer into murine skeletal muscle: a systematic analysis of parameters for long-term gene expression. Technol Cancer Res Treat. 2008;7(2):91–101.
Crossref Google Scholar
21

Bustin SA, Benes V, Garson JA, et al. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem. 2009;55(4):611–622.
Crossref Google Scholar
22

Pfaffl MW, Horgan GW, Dempfle L. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 2002;30(9):e36.
Crossref Google Scholar
23

Mirmira RG, Tager HS. Role of the phenylalanine B24 side chain in directing insulin interaction with its receptor. Importance of main chain conformation. J Biol Chem. 1989;264(11):6349–6354.
Crossref Google Scholar
24

Xie M, Ye H, Wang H, et al. β-cell-mimetic designer cells provide closed-loop glycemic control. Science. 2016;354(6317):1296–1301.
Crossref Google Scholar
25

Miller KM, Beck RW, Foster NC, et al. HbA1c levels in type 1 diabetes from early childhood to older adults: a deeper dive into the influence of technology and socioeconomic status on HbA1c in the T1D exchange clinic registry findings. Diabetes Technol Ther. 2020;22(9):645–650.
Crossref Google Scholar
26

Kilpatrick ES, Bloomgarden ZT, Zimmet PZ. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes: response to the International Expert Committee. Diabetes Care. 2009;32(12):e159.
Crossref Google Scholar
27

Cahill Jr GF. Insulin and proinsulin. N Engl J Med. 1970;283(14):762.
Crossref Google Scholar
28

Realsen JM, Chase HP. Recent advances in the prevention of hypoglycemia in type 1 diabetes. Diabetes Technol Ther. 2011;13(12):1177–1186.
Crossref Google Scholar
29

Kang HM, Kim J, Park S, et al. Insulin-secreting cells from human eyelid-derived stem cells alleviate type Ⅰ diabetes in immunocompetent mice. Stem Cell. 2009;27(8):1999–2008.
Crossref Google Scholar
30

Xiao X, Guo P, Shiota C, et al. Endogenous reprogramming of alpha cells into beta cells, induced by viral gene therapy, reverses autoimmune diabetes. Cell Stem Cell. 2018;22(1):78–90.
Crossref Google Scholar
31

Wang MY, Dean ED, Quittner-Strom E, et al. Glucagon blockade restores functional β-cell mass in type 1 diabetic mice and enhances function of human islets. Proc Natl Acad Sci U S A. 2021;118(9):e2022142118.
Crossref Google Scholar
32

Boisgerault F, Mingozzi F. The skeletal muscle environment and its role in immunity and tolerance to AAV vector-mediated gene transfer. Curr Gene Ther. 2015;15(4):381–394.
Crossref Google Scholar
33

Blaveri K, Heslop L, Yu DS, et al. Patterns of repair of dystrophic mouse muscle: studies on isolated fibers. Dev Dyn. 1999;216(3):244–256.
Crossref
34

Frontera WR, Ochala J. Skeletal muscle: a brief review of structure and function. Calcif Tissue Int. 2015;96(3):183–195.
Crossref Google Scholar
35

Lu QL, Bou-Gharios G, Partridge TA. Non-viral gene delivery in skeletal muscle: a protein factory. Gene Ther. 2003;10(2):131–142.
Crossref Google Scholar
36

Kessler PD, Podsakoff GM, Chen X, et al. Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein. Proc Natl Acad Sci U S A. 1996;93(24):14082–14087.
Crossref Google Scholar
37

Olfert IM, Breen EC, Mathieu-Costello O, et al. Skeletal muscle capillarity and angiogenic mRNA levels after exercise training in normoxia and chronic hypoxia. J Appl Physiol. 2001;91(3):1176–1184.
Crossref Google Scholar
38

Tripathy SK, Svensson EC, Black HB, et al. Long-term expression of erythropoietin in the systemic circulation of mice after intramuscular injection of a plasmid DNA vector. Proc Natl Acad Sci U S A. 1996;93(20):10876–10880.
Crossref Google Scholar
39

Hou WR, Xie SN, Wang HJ, et al. Intramuscular delivery of a naked DNA plasmid encoding proinsulin and pancreatic regenerating Ⅲ protein ameliorates type 1 diabetes mellitus. Pharmacol Res. 2011;63(4):320–327.
Crossref Google Scholar
40

Vakilian M, Tahamtani Y, Ghaedi K. A review on insulin trafficking and exocytosis. Gene. 2019;706:52–61.
Crossref Google Scholar
41

Wolff JA, Malone RW, Williams P, et al. Direct gene transfer into mouse muscle in vivo. Science. 1990;247(4949 Pt 1):1465–1468.
Crossref Google Scholar
42

Wells DJ. Gene therapy progress and prospects: electroporation and other physical methods. Gene Ther. 2004;11(18):1363–1369.
Crossref Google Scholar
43

Rincon MY, Sarcar S, Danso-Abeam D, et al. Genome-wide computational analysis reveals cardiomyocyte-specific transcriptional cis-regulatory motifs that enable efficient cardiac gene therapy. Mol Ther. 2015;23(1):43–52.
Crossref Google Scholar
44

Escobar H, Schöwel V, Spuler S, et al. Full-length dysferlin transfer by the hyperactive sleeping beauty transposase restores dysferlin-deficient muscle. Mol Ther Nucleic Acids. 2016;5(1):e277.
Crossref Google Scholar
45

Home PD. The pharmacokinetics and pharmacodynamics of rapid-acting insulin analogues and their clinical consequences. Diabetes Obes Metab. 2012;14(9):780–788.
Crossref Google Scholar
46

Heinemann L, Heise T, Wahl LC, et al. Prandial glycaemia after a carbohydrate-rich meal in type Ⅰ diabetic patients: using the rapid acting insulin analogue [Lys(B28), Pro(B29)] human insulin. Diabet Med. 1996;13(7):625–629.
Crossref
47

Garg SK, Wernicke-Panten K, Wardecki M, et al. Efficacy and safety of insulin aspart biosimilar SAR341402 versus originator insulin aspart in people with diabetes treated for 26 weeks with multiple daily injections in combination with insulin glargine: a randomized open-label trial (GEMELLI 1). Diabetes Technol Ther. 2020;22(2):85–95.
Crossref Google Scholar
48

Zhou Y, Kong D, Wang X, et al. A small and highly sensitive red/far-red optogenetic switch for applications in mammals. Nat Biotechnol. 2022;40(2):262–272.
Crossref Google Scholar
Genes & Diseases
Volume 10 Issue 3,
May 2023
Pages 1101-1113
DOI: 10.1016/j.gendis.2022.05.009
Cite this article:
Deng L, Yang P, Li C, et al. Prolonged control of insulin-dependent diabetes via intramuscular expression of plasmid-encoded single-strand insulin analogue. Genes & Diseases, 2023, 10(3): 1101-1113. https://doi.org/10.1016/j.gendis.2022.05.009

311

Views

5

Downloads

6

Crossref

8

Web of Science

6

Scopus

0

CSCD

Altmetrics
Received: 11 January 2022
Revised: 27 April 2022
Accepted: 11 May 2022
Published: 24 May 2022
© 2022 The Authors.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Return