Selective delivery of interleukine-1 receptor antagonist to inflamed joint by albumin fusion
Authors: Mengyuan Liu
Guoping Liu
Xiaosong Yang
Lei Hu
Dongxu Liu
Xueping Hu
Yi Huang
Journal: BMC Biotechnology (2012)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Interleukin-1 receptor antagonist; albumin; drug delivery; genetic fusion; recombinant protein
Affiliations: Center for Infection and Immunity Research, School of Life Sciences, Hubei University, Youyi Road 368, Wuhan 430062, China. 

Abstract:  Background: Interleukin-1 receptor antagonist, a cytokine that is highly therapeutic to rheumatoid arthritis and several other inflammatory diseases, exhibits rapid blood clearance and poor retention time on the target in clinical application due to its small size and lack of specificity to target tissue. Albumin has been widely employed as macromolecular carrier for drug delivery purpose to extend the plasma half-life of therapeutic molecules and has been shown to selectively accumulate and to be metabolized in the inflamed joints of patients with rheumatoid arthritis. This suggests that genetic fusion of IL-1ra to albumin can probably overcome the drawbacks of in vivo application of IL-1ra. Result: A recombinant protein, engineered by fusing human serum albumin (HSA) to the carboxyl terminal of IL-1ra, was produced in Pichia pastoris and purified to homogeneity. The fusion protein retained the antagonist activity of IL-1ra and had a plasma half-life of approximately 30-fold more than that of IL-1ra in healthy mice. In vivo bio-distribution studies demonstrated that the fusion protein selectively accumulated in arthritic paws for a long period of time in mice with collagen-induced arthritis, showing low uptake rates in normal organs such as liver, kidney, spleen and lung in contrast to IL-1ra alone. Moreover, this fusion protein was able to significantly improve the therapeutic efficacy of IL-1ra in collagen-induced arthritis mouse model. Conclusions: The fusion protein described here, able to selectively deliver IL-1ra to inflamed tissue, could yield important contributions for the therapy of rheumatoid arthritis and other inflammatory diseases. 

Retracted: No

PubPeer comments:
  Figure 3. Inhibition of HAS1 suppresses cell motility. KYSE70 and EC109 cell lines were transfected with HAS1-siRNA or siRNA scramble, respectively. (A) Transwell invasion assay was conducted to observe the invasive cells in KYSE70 and EC109 cells.  ![file] Possibly this figure was a test to see if any of the peer reviewers at IJO were paying attention. , 
 #1 After rotation, the HAS1-siRNA panels reward comparison with the LV-MEG3 panels of Fig 2C and FIg 4A from [Li et al (2018)] . ![file] ![file] A detail manifested in Fig 2A of [Gu et al (2019)] . ![] , 
 Please be noted, the same or very similar crease of Surgical pad are showing on the following 11 chinese papers including this paper. Also, the samples on the pad are somehow shared in those papers. UCA1 Regulates the Growth and Metastasis of Pancreatic Cancer bySponging miR-135a. Oncology research (2017) . DOI: 10.3727 096504017x14888987683152. ![file] H19 promotes the migration and invasion of colon cancer by spongingmiR-138 to upregulate the expression of HMGA1. INTERNATIONAL JOURNAL OF ONCOLOGY (2017). DOI: 10.3892 ijo.2017.3941. ![file] Silencing of lncRNA CCDC26 Restrains the Growth and Migration of Glioma Cells In Vitroand In Vivo via Targeting miR-203. Oncology research (2018). DOI: 10.3727 096504017x14965095236521. ![file] Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancervia Targeting miR-198 and Promoting the MAPK1 Pathway. Oncology research (2018) . DOI: 10.3727 096504017x14944585873631. ![file] HOTAIR contributes to cell proliferation and metastasis of cervical cancer via targetting MAPK1 axis. Bioscience reports (2018). DOI: 10.1042 bsr20171563. ![file] Long non-coding RNA MEG3 inhibits cell growth of gliomas by targeting miR-93 andinactivating PI3K AKT pathway. Oncology reports (2017). DOI: 10.3892 or.2017.5871. ![file] The inhibitory effect of MEG3 miR-214 AIFM2 axis on the growth of T-cell lymphoblastic lymphoma. INTERNATIONAL JOURNAL OF ONCOLOGY. DOI: 10.3892 ijo.2017.4006. ![file] Inhibition of BAMBI reduces the viability and motility of colon cancervia activating TGFu2011u03b2 Smad pathway in vitro and in vivo. ONCOLOGY LETTERS. 10.3892 ol.2017.6811. ![file] HNF1Au2011AS1 promotes growth and metastasis of esophageal squamous cellcarcinoma by sponging miRu2011214 to upregulate the expression of SOX-4. INTERNATIONAL JOURNAL OF ONCOLOGY. DOI: 10.3892 ijo.2017.4034. ![file] Astragaloside IV inhibits progression of glioma via blocking MAPK ERKsignaling pathway. Biochemical and Biophysical Research Communications (2017). DOI: 10.1016 j.bbrc.2017.07.052. ![file] Epigenetic silence of HOTAIR contributes to the metastasis of pancreaticcancer via targeting miR-138. Oncology Research (2017). DOI: 10.3727 096504017X15138544374391. ![file] Possibly the following one: Long Noncoding RNA MEG3 Inhibits Cell Proliferation and Metastasis in Chronic Myeloid Leukemia via Targeting miR-184. Oncology research (2018) . DOI: 10.3727 096504017x14980882803151 ![file] , 
 A scatterplot based on the same points is used in Fig 5E of [Li et al (2018)] , Fig 6D of [Zhang et al (2017)] , Fig 1C of [Chen et al (2019)] , Fig 3K of [Yang et al (2017)] , Fig 7A of [Fan et al (2017)] and Fig 5H of [Wang et al (2017)] . ![file] This deserves some sort of award. , 
 Retracted [11 January 2021] . ------------------------------ Following the publication of this paper, it was drawn to the authors attention by an interested reader that the Transwell invasion assay images in Fig. 3A had been duplicated and re-presented within the same Figure. Furthermore, the same data were strikingly similar, in spite of their different presentation, to data featured in Fig. 2A of an article appearing in Oncology Research [Gu J, Cui, C-F, Yang, L, Wang L and Jiang X-H: Emodin inhibits colon cancer cell invasion and migration by suppressing epithelial-mesenchymal transition via the Wnt u03b2-catenin pathway. Oncol Res 27: 193-202, 2019]. Finally, some of the tumour images featured in Fig. 6A of the above paper were strikingly similar to those featured in several other publications. The Editor asked the authors for an explanation to account for the appearance of strikingly similar data in their paper independently, and they responded to request that the paper be retracted from International Journal of Oncology. All the authors agreed that the article should be retracted. The Editor apologizes to the readership for any inconvenience caused. ,