Nucleic Acid Nanotheranostics: Biomedical Applications

“Biologics” have come of age in clinics, as biochemical modulators for humans and animal disorders and to date have had minimal offtarget consequences. For this treatise, the term “biologics” refer to larger biologically produced polymers or assemblies, such as proteins, lipids and nucleic acids (DNA and RNA). Their origin dates back the late 18th century when Edward Jenner used the bovine vaccinia virus to induce acquired human immunity to the smallpox virus. Vaccines have since become principle defenses against viral and bacterial pathogens as evidenced by the current investments in preventing infection from approximately 110 different human pathogens. Another early “biologic” was insulin, isolated from cattle and pigs for the treatment of type 1 diabetes. In the early 1980s, with the advent of modern molecular biology technologies that allowed for the manipulation and expression of gene sequences, active enzymes became clinically available for treating individuals suffering from certain genetic disorders. One such commercial product, produced by Genzyme, Ceredase, is used in enzyme replacement therapy to treat the lysosomal storage disorder Gaucher disease type 1. As of 2016 seven other enzymes are now used clinically, including mucopolysaccharidosis type II, Fabry disease, Pompe disease, Maroteaux-Lamy syndrome, Morquio A syndrome, and Lysosomal acid lipase disease. These therapies involve the periodic infusion of the isolated enzyme, usually at great financial expense. Gene therapy would be the analogous approach for genetic disorders, such as the inborn errors of metabolism mentioned above. The safe and efficient delivery of nucleic acids to patients has the potential of shifting the paradigm on controlling these diseases and others. Unfortunately, the proposed use of gene therapy has not lived up to its initial promise due to numerous obstacles. Nearly all of the approved gene therapy trials used virus particles to deliver the corrective nucleic acid sequences. Many of the problems stem from host reactions to the vectors (adenovirus, adeno-associated virus, herpes virus, lentivirus, and retrovirus) used to deliver the genetic material. These include liver toxicity, transient expression, lack