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Optimizing delivery for efficient cardiac reprogramming.

Publication ,  Journal Article
Kang, MH; Hu, J; Pratt, RE; Hodgkinson, CP; Asokan, A; Dzau, VJ
Published in: Biochem Biophys Res Commun
November 26, 2020

Following heart injury, cardiomyocytes, are lost and are not regenerated. In their place, fibroblasts invade the dead tissue where they generate a scar, which reduces cardiac function. We and others have demonstrated that combinations of specific miRNAs (miR combo) or transcription factors (GMT), delivered by individual lenti-/retro-viruses in vivo, can convert fibroblasts into cardiomyocytes and improve cardiac function. However, the effects are relatively modest due to the low efficiency of delivery of miR combo or GMT. We hypothesized that efficiency would be improved by optimizing delivery. In the first instance, we developed a multicistronic system to express all four miRNAs of miR combo from a single construct. The order of each miRNA in the multicistronic construct gave rise to different levels of miRNA expression. A combination that resulted in equivalent expression levels of each of the four miRNAs of miR combo showed the highest reprogramming efficiency. Further efficiency can be achieved by directly targeting fibroblasts. Screening of several AAV serotypes indicated that AAV1 displayed tropism towards cardiac fibroblasts. Combining multicistronic expression with AAV1 delivery robustly reprogrammed cardiac fibroblasts into cardiomyocytes in vivo.

Duke Scholars

Published In

Biochem Biophys Res Commun

DOI

EISSN

1090-2104

Publication Date

November 26, 2020

Volume

533

Issue

1

Start / End Page

9 / 16

Location

United States

Related Subject Headings

  • Transfection
  • Plasmids
  • Myocytes, Cardiac
  • Myocardial Infarction
  • MicroRNAs
  • Mice, Inbred C57BL
  • Male
  • Fibroblasts
  • Dependovirus
  • Cellular Reprogramming Techniques
 

Citation

APA
Chicago
ICMJE
MLA
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Kang, M. H., Hu, J., Pratt, R. E., Hodgkinson, C. P., Asokan, A., & Dzau, V. J. (2020). Optimizing delivery for efficient cardiac reprogramming. Biochem Biophys Res Commun, 533(1), 9–16. https://doi.org/10.1016/j.bbrc.2020.08.104
Kang, Martin H., Jiabiao Hu, Richard E. Pratt, Conrad P. Hodgkinson, Aravind Asokan, and Victor J. Dzau. “Optimizing delivery for efficient cardiac reprogramming.Biochem Biophys Res Commun 533, no. 1 (November 26, 2020): 9–16. https://doi.org/10.1016/j.bbrc.2020.08.104.
Kang MH, Hu J, Pratt RE, Hodgkinson CP, Asokan A, Dzau VJ. Optimizing delivery for efficient cardiac reprogramming. Biochem Biophys Res Commun. 2020 Nov 26;533(1):9–16.
Kang, Martin H., et al. “Optimizing delivery for efficient cardiac reprogramming.Biochem Biophys Res Commun, vol. 533, no. 1, Nov. 2020, pp. 9–16. Pubmed, doi:10.1016/j.bbrc.2020.08.104.
Kang MH, Hu J, Pratt RE, Hodgkinson CP, Asokan A, Dzau VJ. Optimizing delivery for efficient cardiac reprogramming. Biochem Biophys Res Commun. 2020 Nov 26;533(1):9–16.
Journal cover image

Published In

Biochem Biophys Res Commun

DOI

EISSN

1090-2104

Publication Date

November 26, 2020

Volume

533

Issue

1

Start / End Page

9 / 16

Location

United States

Related Subject Headings

  • Transfection
  • Plasmids
  • Myocytes, Cardiac
  • Myocardial Infarction
  • MicroRNAs
  • Mice, Inbred C57BL
  • Male
  • Fibroblasts
  • Dependovirus
  • Cellular Reprogramming Techniques