Intracellular Delivery of Proteins with Cell-Penetrating Peptides for Therapeutic Uses in Human Disease

• Published in: International journal of molecular sciences Vol. 17; no. 2; p. 263
• Main Authors: Dinca, Ana, Chien, Wei-Ming, Chin, Michael T
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22-02-2016; MDPI
• Subjects: Animals; Cell Membrane - metabolism; cell-penetrating peptides (CPPs); Cell-Penetrating Peptides - administration & dosage; Cell-Penetrating Peptides - chemistry; Clinical Trials as Topic; Drug Carriers - administration & dosage; Drug Carriers - chemistry; enzyme deficiency; enzyme replacement therapy (ERT); Enzymes; Humans; Molecular biology; Peptides; protein therapeutics; Protein Transport; Recombinant Proteins - chemistry; Recombinant Proteins - therapeutic use; Review; cell-penetrating peptides (CPPs); enzyme deficiency; protein therapeutics; enzyme replacement therapy (ERT)
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms17020263

Protein therapy exhibits several advantages over small molecule drugs and is increasingly being developed for the treatment of disorders ranging from single enzyme deficiencies to cancer. Cell-penetrating peptides (CPPs), a group of small peptides capable of promoting transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular uptake of exogenously delivered proteins. Although the molecular mechanisms of uptake are not firmly established, CPPs have been empirically shown to promote uptake of various molecules, including large proteins over 100 kiloDaltons (kDa). Recombinant proteins that include a CPP tag to promote intracellular delivery show promise as therapeutic agents with encouraging success rates in both animal and human trials. This review highlights recent advances in protein-CPP therapy and discusses optimization strategies and potential detrimental effects.