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Intron-mediated enhancement of SPINK1 expression for pancreatitis therapy
  1. Gergő Berke,
  2. Miklós Sahin-Tóth
  1. Department of Surgery, University of California, Los Angeles, California, USA
  1. Correspondence to Dr Miklós Sahin-Tóth, Department of Surgery, University of California Los Angeles, Los Angeles, California, USA; msahintoth{at}

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We have read with great interest and excitement the article by Wang et al,1 in which the authors demonstrated that pancreatic overexpression of the human trypsin inhibitor SPINK1 (serine protease inhibitor Kazal type 1, also known as pancreatic secretory trypsin inhibitor) via an adeno-associated viral (AAV) vector significantly improved pancreatitis severity and outcomes in preclinical mouse models.1 This seminal study provides proof of concept that AAV-mediated delivery of trypsin inhibitors to the pancreas is a viable strategy for the treatment of pancreatitis and/or prevention of recurrent attacks. A limitation of the approach, however, is the relatively low expression levels of SPINK1 attainable in the pancreas. In the cited study, pancreatic trypsin-inhibitory activity and SPINK1 protein levels were elevated only by 1.4-fold and 1.6-fold, respectively, after viral transduction. Further increases in the viral dose employed may not be feasible due to cost and higher risk of side effects.

Here, using a cell culture model, we demonstrate that introducing a short intronic sequence into the human SPINK1 coding DNA (cDNA) resulted in dramatic increases in mRNA and protein expression levels. Studies conducted in a variety of eukaryotes showed that introns can boost gene expression, a phenomenon referred to …

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  • Contributors Study concept and design: MS-T. Experiments: GB. Acquisition, analysis or interpretation of data: both authors. Drafting of the manuscript: MS-T. Critical revision of the manuscript for important intellectual content: both authors. Obtained funding: MS-T. Administrative, technical or material support: both authors. Study supervision: MS-T. Final approval of manuscript as submitted: both authors. Guarantor of the article: MS-T.

  • Funding This study was supported by the National Institutes of Health (NIH) grants R01 DK117809 and R01 DK082412 to MS-T.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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