Delivery of nucleic acids and nanomaterials by cell-penetrating peptides: opportunities and challenges.

Yue-Wern Huang,Larry M Tolliver,Han-Jung Lee,Robert S Aronstam

doi:10.1155/2015/834079

Abstract

Many viral and nonviral systems have been developed to aid delivery of biologically active molecules into cells. Among these, cell-penetrating peptides (CPPs) have received increasing attention in the past two decades for biomedical applications. In this review, we focus on opportunities and challenges associated with CPP delivery of nucleic acids and nanomaterials. We first describe the nature of versatile CPPs and their interactions with various types of cargoes. We then discuss in vivo and in vitro delivery of nucleic acids and nanomaterials by CPPs. Studies on the mechanisms of cellular entry and limitations in the methods used are detailed.

Highlights

The first Cell-penetrating peptide CDK9 (CPP) was discovered by two independent groups and is comprised of a protein transduction domain (PTD) derived from the transactivator of transcription (Tat) of the human immunodeficiency virus type 1 (HIV-1) [2, 3]
In addition to penetrating cytoplasmic membrane and nucleus, we demonstrated that a CPP-piggyBac transposase (CPP-PBase) plasmid system could accomplish both protein transduction and transposition [101]
CPPs are capable of carrying nucleic acids and nanomaterials into cells

Summary

Introduction

The plasma membrane plays essential roles in selective permeability, osmotic balance, compartmentalization, and cellular uptake Small polar molecules such as ions, amino acids, and sugars enter cells through specific carriers and channels in the membrane. Delivery tools have been developed to facilitate cellular uptake of large molecules for basic research and biomedical applications (Figure 1) These include mechanical and electrical transfection techniques such as microinjection, bioballistics, hydrodynamic force, ultrasonic nebulization, electroporation, chemical/biochemical methods such as calcium phosphate coprecipitation, membrane fusion catalyzed by artificial lipids, peptides/proteins, dendrimers, adenovirusassociated virus vectors, and lentiviral vectors [1]. The first CPP was discovered by two independent groups and is comprised of a protein transduction domain (PTD) derived from the transactivator of transcription (Tat) of the human immunodeficiency virus type 1 (HIV-1) [2, 3] This domain contains eleven amino acids (YGRKKRRQRRR) that are responsible for cellular entry of Tat [4]. CLIKKALAALAKLNIKLLYGASNLTWG GLWRALWRLLRSLWRLLWRA RLLRLLLRLWRRLLRLLR RLWRLLWRLWRRLWRLLR LLKLLKKLLKLLKKLLKLL KALKLKLALALLAKLKLA Stearyl-KALKLKLALALLAKLKLA GGG[ARKKAAKA]4

CPPs Delivery of Nucleic Acids

CPPs Delivery of Nanomaterials

Mechanisms of CPP-Mediated Cellular Uptake

Conclusions

Conflict of Interests