What is Gene Therapy?

Gene therapy is a novel type of medicine where genetic material is introduced into cells to correct abnormal genes. Genes can be inserted in living human cells via various vehicles, also known as vectors, such as viral vectors, bacterial vectors or plasmid DNA. Functional genes are delivered to target cells in the human body to restore normal functioning of abnormal genes.


  • Viral vectors: Viruses have natural ability to deliver genetic material into host cells. Owing to this ability, viruses are often modified to carry therapeutic genes into affected cells, thus making them ideal for gene therapy.
  • Bacterial vectors: Modified bacteria are also used to carry therapeutic genes into target cells to prevent the target human cells from causing infectious disease.
  • Plasmid DNA: Circular (plasmid) DNA molecules can be modified to carry therapeutic genes into affected cells.


How is Gene Therapy manufactured?

Gene therapy manufacturing can be broadly divided into three phases: upstream processing, in which vectors and therapeutic genes are produced; downstream processing, through which vectors and therapeutic genes are purified; and formulation processing, where vectors containing therapeutic genes are formulated into a final injectable gene therapy product.

Raw materials and excipients manufactured under full GMP compliance are essential to avoid carryover of impurities into the finished therapeutic good and to ensure the materials won’t pose any risk to the safety and efficacy of the final gene therapy product.


1. Gene therapy upstream processing: This step starts with cell culture media preparation to grow vector viruses and cells. These are essential in delivering therapeutic genes to target human cells. To obtain safe and efficacious vectors and therapeutic genes, the use of GMP grade excipients is preferred in upstream processing of gene therapy.

Types of raw materials used in upstream processes of gene therapy manufacturing include:

  • Energy source – Media requires carbohydrates such as GMP grade Sucrose to provide necessary energy to allow growth of viral vectors and/or therapeutic genes.
  • Minerals and salts – Inorganic salts are used to maintain required tonicity of growth media. GMP grade Sodium Chloride is widely used as an inorganic salt in upstream processing.


2. Gene therapy downstream processing: Once vectors and therapeutic genes are obtained in sufficient quantities, they are filtered from cell debris. Viral vectors are then loaded with therapeutic genes to obtain pure biologically active gene therapy ingredients. Purification is crucial as it directly affects efficacy and safety of the final formulation.

Types of raw materials used in downstream processes of gene therapy manufacturing include:

  • Lysing/purification agents – These are used to bring about cell lysis to obtain therapeutic genes. GMP grade PMSF is a widely used lysing agent in gene therapy manufacturing.
  • Buffers – These are critical in maintaining the required pH range of media. Some of the buffers employed in gene therapy manufacturing include a variety of phosphate buffers, GMP grade Tris HCL and Tris Base buffers.


3. Formulation processing:

To manufacture a stable, safe and efficacious gene therapy formulation, a variety of GMP grade excipients are employed. These GMP grade excipients play several roles including that of stabilizing agents, tonicity adjusters, lyoprotectants and preservatives.

Types of raw materials used in gene therapy formulation include:

  • Stabilizing agents – These agents are used to stabilize inherently unstable proteins and other biological substances. Some of the stabilizing agents used in final gene therapy formulations are GMP grades of PEG 400, Polysorbate 80 and DMSO.
  • Preservatives – These are often used in gene therapy formulations to prevent pathogenic growth of bacteria and fungi. Widely used preservatives include GMP grades of 2-Phenoxyethanol, Thimerosal, Benzalkonium Chloride, Phenol liquefied and Formaldehyde.
  • Tonicity adjusters – Gene therapy formulations are required to be isotonic to bodily fluids at the site of administration. GMP grades of Sodium Chloride and Calcium Chloride are generally used to adjust tonicity.
  • Lyoprotectants – These are the agents used to prevent degradation of biologically active genes when undergoing lyophillization. GMP grade Sucrose is an example of a lyoprotectant widely used in gene therapy formulations.



Why are GMP grade excipients preferred in gene therapy manufacturing?


  • Compendial grade: GMP grade such as compendial grade excipients conform to well established standards laid out in pharmacopoeias such as USP, EP, BP and JP. These rigorous compendial standards ensure the highest possible quality products.
  • Consistency and traceability: GMP grade excipients provide consistency and traceability of raw materials going into manufacturing processes and final gene therapy formulations. From a biopharmaceutical quality perspective, consistency and traceability are crucial in establishing robustness of manufacturing processes and quality of products.
  • Supply assurance and compliance: Gene therapy products utilize a variety of ingredients and require stable quality supply of ingredients while conforming to regulations.
  • GMP compliant packaging (suitable packaging material): GMP grade packaging and repacking is crucial to maintain compendial quality of excipients. Packing material must conform to GMP packaging standards to ensure safe and efficient usage in final formulations.


A&C has been servicing the biopharmaceutical market for more than 50 years. We supply a wide range of GMP grade excipients, intermediates and process solutions to gene therapy manufacturers around the world. Our GMP raw materials are used in a variety of novel gene therapy products by some of the world’s leading biopharmaceutical companies.


We also provide GMP custom development of niche and novel excipients, GMP custom manufacturing, and GMP packaging & repacking of liquid and powder raw materials. At A&C, we offer tailor-made GMP solutions for excipients and raw materials, from early-stage formulation development to late-stage commercial scale supply.


Glossary of acronyms:

GMP – Good Manufacturing Practice

DNA – Deoxyribonucleic Acid

Tris – Tromethamine Hydrochloride

PEG 400 – Polyethylene Glycol 400

DMSO – Dimethyl Sulfoxide

USP – United States Pharmacopeia

EP – European Pharmacopoeia

BP – British Pharmacopoeia

JP – Japanese Pharmacopoeia

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