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Systemically Administered, Target-Specific, Multi-Functional Therapeutic Recombinant Proteins in Regenerative Medicine

Faculty of Medicine & Health Technology, Tampere University, FI-33014 Tampere, Finland & Tampere University Hospital, 33520 Tampere, Finland
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Nanomaterials 2020, 10(2), 226; https://doi.org/10.3390/nano10020226
Received: 17 December 2019 / Revised: 21 January 2020 / Accepted: 24 January 2020 / Published: 28 January 2020
(This article belongs to the Special Issue Protein Nanostructures for Biomedical Applications)
Growth factors, chemokines and cytokines guide tissue regeneration after injuries. However, their applications as recombinant proteins are almost non-existent due to the difficulty of maintaining their bioactivity in the protease-rich milieu of injured tissues in humans. Safety concerns have ruled out their systemic administration. The vascular system provides a natural platform for circumvent the limitations of the local delivery of protein-based therapeutics. Tissue selectivity in drug accumulation can be obtained as organ-specific molecular signatures exist in the blood vessels in each tissue, essentially forming a postal code system (“vascular zip codes”) within the vasculature. These target-specific “vascular zip codes” can be exploited in regenerative medicine as the angiogenic blood vessels in the regenerating tissues have a unique molecular signature. The identification of vascular homing peptides capable of finding these unique “vascular zip codes” after their systemic administration provides an appealing opportunity for the target-specific delivery of therapeutics to tissue injuries. Therapeutic proteins can be “packaged” together with homing peptides by expressing them as multi-functional recombinant proteins. These multi-functional recombinant proteins provide an example how molecular engineering gives to a compound an ability to home to regenerating tissue and enhance its therapeutic potential. Regenerative medicine has been dominated by the locally applied therapeutic approaches despite these therapies are not moving to clinical medicine with success. There might be a time to change the paradigm towards systemically administered, target organ-specific therapeutic molecules in future drug discovery and development for regenerative medicine. View Full-Text
Keywords: vascular homing peptide; cell penetrating peptide; angiogenesis; vascular heterogeneity; fibrosis; targeted delivery; decorin; transforming growth factor-β (TGF-β); bystander effect; CendR peptide; tissue regeneration; regenerative medicine; hypoxia; neuropilin-1; stem cell vascular homing peptide; cell penetrating peptide; angiogenesis; vascular heterogeneity; fibrosis; targeted delivery; decorin; transforming growth factor-β (TGF-β); bystander effect; CendR peptide; tissue regeneration; regenerative medicine; hypoxia; neuropilin-1; stem cell
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MDPI and ACS Style

Järvinen, T.A.; Pemmari, T. Systemically Administered, Target-Specific, Multi-Functional Therapeutic Recombinant Proteins in Regenerative Medicine. Nanomaterials 2020, 10, 226.

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