Introduction to Gene Therapy

Recently, gene therapy has become a hot topic in the biomedical research and pharmaceutical industry because the timeline of new drug approval for the US Food and Drug Administration (FDA) is shorter than traditional drug modalities, such as small molecular drugs. In addition, after the COVID pandemic, gene-based technology plays an important role in vaccine development with its advantage in completing the clinical trial for new drug applications (IND). Taking Moderna as an example, after Chinese authorities shared the genetic sequence of the COVID, the National Institute of Health (NIH) and Moderna finalized the sequence for its mRNA product for the COVID vaccine. Moreover, Moderna began the clinical trial in April 2020 and received the emergency use of its mRNA vaccine (mRNA-1273) for COVID-19 from the FDA in December. This is a great example to show how fast gene therapy could be approved and authorized by FDA.

Before discussing the types of gene therapy, I would like to briefly introduce nucleic acid, which is an essential sugar-based biomolecule in all cells and viruses. Nucleic acids are divided into two famous classes, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). These nucleic acids store pieces of information in the cells and also passage this information to our descendants. Moreover, the DNA is composed of 4 different units, Adenine (A), Thymine (T), Cytosine (C), and Guanine (G), and RNA is composed of Adenine (A), Uracil (U), Cytosine (C) and Guanine (G). DNA can transcript into RNA in the cells and then translate into protein to work for the cells. For example, the mechanism of the COVID vaccine from Johnson& Johnson or AstraZeneca is to deliver the DNA sequence of spike protein in coronavirus by adenovirus. When the DNA fragment is given in the cells, it will transcript into mRNA and translation into the spike protein. So the immune system could recognize the proteins and produce antibodies to protect the body if any coronavirus is found. In the mRNA vaccine, the mechanism is straightforward because the targeted mRNA could directly deliver to the cells and produce the proteins.

Figure to illustrate how DNA convert into RNA and translate into proteins

Up to date, there are two types of gene therapy, virus-based, and non-virus-based delivery system. In a virus-based delivery system, adenovirus and adeno-associated virus (AAV) are the primary vehicles to deliver nucleic acids. In the COVID vaccines, two companies (AstraZeneca and Johnson&Johnson) used adenovirus to deliver the DNA sequence of spike protein on coronavirus. Also, there are two FDA-approved AAV-based therapies: First, Spark Therapeutics developed Luxturna for degenerative disease of the eye (retinal dystrophy). Second, Novartis uses Zolgensma to treat spinal muscular atrophy (type I). On the other hand, the non-viral system mainly focuses on synthetic materials, such as polymeric materials, ionizable lipids, peptides, and zwitterionic lipids and dendrimers. In the early research, scientists focused on cationic materials to form nanoparticles with nucleic acids; however, researchers have recently worked on pH-dependent ionizable materials with lower toxicity. In an acidic environment, the ionizable materials become cationic and form nanoparticles with anionic nucleic acids by electrostatic force. These ionizable materials could protect the therapeutic mRNA from degradation and selectively target the specific cells for delivery. Additionally, after the lipid nanoparticles enter the cells, the mRNA would be released in a neutral cytoplasm environment where the mRNA would start to translate into protein to treat disease or build up the protection from any virus or bacteria. Since the mRNA-based vaccine for COVID, the non-viral system for mRNA delivery has become a popular field in gene therapy development.

Illustrate how COVID (AstraZeneca) vaccine works in the body

In sum, with the fast developing timeline, gene therapy would be a major modality in pharmaceutical companies in the next decade and also benefit human health welfare, such as vaccine development in different viruses.


  1. P. Kowalski et. al., “Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery.”, Molecular Therapy Vol. 27, No. 4, 2019
  2. S. Liu et. al., “Membrane-destabilizing ionizable phospholipids for organ-selective mRNA delivery and CRISPR-Cas gene editing.”, Nature Materials Vol. 20, 2021

Jason(Yen-Chun) Lu, All right reserved.

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