Eliminating the six N-terminal amino acids of the caspase 3 large subunit improved production of a biologically active IL2-Caspase3 chimeric protein

Yitav Glantz, Ofra Sabag, Michal Lichtenstein, Inna Grodzovski, Haya Lorberboum-Galski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Designing a chimeric protein and developing a procedure for its stable production as a biologically active protein, are key steps in its potential application to clinical trails. IL2-Caspase3 chimeric protein designed to target activated T lymphocytes was found to be a promising molecule for targeted treatment, however was found to be difficult to produce as a biological active molecule. Thus, we designed a new version of the molecule, IL2-Caspase3s, in which six amino acids (aa 29-34) from the N-terminus of the large subunit of caspase 3 were excluded. Repeated expressions, productions, and partial purifications of the IL2-Caspase3s yielded reproducible batches with consistent results. We found that IL2-Caspase3s causes cell death in a specific, dose-, and time-dependent manner. Cell death due to IL2-Caspase3s is caused by apoptosis. This improved and biologically stable IL2-Caspase3s chimeric protein may be developed in the future for clinical trails as a promising therapy for several pathologies involving activated T-cells. Moreover, this truncated caspase 3 sequence, lacking the N-terminal six amino acids of its large subunit, may be used in other caspase 3-based chimeric proteins targeted against various human diseases, using the appropriate targeting moiety.

Original languageAmerican English
Pages (from-to)573-580
Number of pages8
JournalBiotechnology Progress
Volume28
Issue number2
DOIs
StatePublished - Mar 2012

Keywords

  • Apoptosis
  • Caspase 3
  • Chimeric protein
  • Interleukin-2 (IL2)

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