Nucleic acid therapeutics have emerged as a powerful method for treatment of many diseases. However, the challenge lies in safe and efficient delivery of nucleic acids to their target site, as they need to cross various extracellular and intracellular barriers. Mammalian viruses have initially been favored for delivery of nucleic acid therapeutics, but safety concerns regarding their immunogenicity and potential of integration have fueled the search for alternative delivery strategies. For example, chemistry and bioengineering have led to advances in the use of nonviral vectors composed of lipids and other polymers; nevertheless, the synthetic systems often do not match the efficiency achieved using the biological systems. More recently, researchers have turned toward the development of plant viruses and bacteriophages and virus-like particles as an alternative or complementary approach. These systems unite the properties of both the viral and nonviral systems and as such are a new exciting avenue toward nucleic acid delivery. This review highlights the benefits of plant viral and bacteriophage delivery of nucleic acids and provides a summary of the current progress in research in this field. © 2017 Wiley Periodicals, Inc.
How to cite this article:WIREs Nanomed Nanobiotechnol 2018, 10:e1487. doi: 10.1002/wnan.1487
NUCLEIC ACID THERAPEUTICS: OPPORTUNITIES AND CHALLENGESN ucleic acid-based therapeutics are comprised of wide-ranging forms of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). Therapeutic use of nucleic acids has had a long history, beginning with gene delivery, and its initial conceptualization over 40 years ago. 1 Since then, there has been an extensive body of work dedicated to gene therapy for treatment of diseases, such as Parkinson's, 2 cystic fibrosis, 3 hemophilia, 4 and cancer. 5 The discovery of small noncoding RNAs that regulate gene expression, 6 has led to the use of microRNAs (miRNAs) and small interfering RNAs (siRNAs) as possible therapeutics. 7 Nucleic acid-based therapies are on the horizon to become a clinical reality: the first approved RNA-based therapy in the market, Macugen, targets vascular endothelial growth factor (VEGF) in the eye to treat neovascular age-related macular degeneration. 8 UniQure's Glybera was approved for clinical use in Europe in 2012. 9 The adeno-associated virus (AAV)-based therapy is used to treat patients with lipoprotein lipase deficiency, an orphan metabolic disorder associated with increased levels of fat in the blood. Other nucleic acid-based therapies are poised to push toward commercialization in the coming year. 10,11 The road to bring gene
of 18therapy to the market has not been an easy one, with tragedy striking in 1999 when a patient died during a clinical trial from adverse immune response instigated by the adenoviral vector meant to correct for ornithine transcarbamylase metabolic deficiency. 12 A few years later, despite great success for many children, retrovirus-based gene treatment for X-linked severe combined immunodeficiency resul...