Gene Therapy Leaves a Vicious Cycle

Abstract

The human genetic code encrypted in thousands of genes holds the secret for synthesis of proteins that drive all biological processes necessary for normal life and death. Though the genetic ciphering remains unchanged through generations, some genes get disrupted, deleted and or mutated, manifesting diseases, and or disorders. Current treatment options-chemotherapy, protein therapy, radiotherapy, and surgery available for no more than 500 diseases-neither cure nor prevent genetic errors but often cause many side effects. However, gene therapy, colloquially called "living drug," provides a one-time treatment option by rewriting or fixing errors in the natural genetic ciphering. Since gene therapy is predominantly a viral vector-based medicine, it has met with a fair bit of skepticism from both the science fraternity and patients. Now, thanks to advancements in gene editing and recombinant viral vector development, the interest of clinicians and pharmaceutical industries has been rekindled. With the advent of more than 12 different gene therapy drugs for curing cancer, blindness, immune, and neuronal disorders, this emerging experimental medicine has yet again come in the limelight. The present review article delves into the popular viral vectors used in gene therapy, advances, challenges, and perspectives.

Keywords: clinical trials; diseases and disorders; gene therapy; modern medicines; viral vectors.

Figure 1

Different methods to deliver therapeutic DNA and proteins to target cells. Non-viral gene delivery methods have many advantages over viral vectors in gene therapy. They do not cause immunogenicity and carcinogenicity, and can deliver a large size of therapeutic DNA efficiently with a low price tag. As no one-size-fits-all solution to therapeutic DNA delivery exits, development, and formulations remain the main focus of research on non-viral methods.

Figure 2

Mechanism of adenovirus-mediated delivery of a therapeutic DNA. Upon infection, adenovirus delivers the encapsulated therapeutic DNA into the cytoplasm of the target cells. Various stages of viral gene delivery, viz cell attachment, internalization, endocytosis, uncoating, transcription and translation of the therapeutic protein, are shown.

Figure 3

Gene therapy drugs in the pharmaceutical market and a timeline of their approval.

Figure 4

Recent trends in gene therapy research and clinical trials. (A) Different diseases being treated by gene therapy in clinical trials. The clinical studies database was searched for the total number of gene therapies conducted in the world to treat different diseases to date. The main focus of the clinical trials was found to be treating cancer, immune, digestive, and genetic diseases. (B) Clinical trials actively recruiting patients for testing gene therapy-mediated medicines in curing diseases. This includes both viral and non-viral vector-mediated gene therapies. A relatively large number of clinical trials are recruiting cancer patients for testing different gene therapy-based medicines. (C) Different recombinant viral vectors being tested in gene therapy-based treatments.