Gene therapy upstream processing

Bioprocessing of gene therapies is the manufacture of vectors used to treat diseases. Upstream vector manufacturing involves multiple steps and processes, including:

• Plasmid production
• Cell expansion
• Infection or transfection of the vector producing cells
• Production of vectors

Different bioprocessing systems are used along with the chosen virus and cell line, depending on the therapeutic application. Other factors considered during gene therapy development include:

• Cost of goods
• Development timeline
• Expected product yield
• Time to market

A gene therapy viral vector is a virus that has been modified to deliver therapeutic encoded genes, regulatory RNAs, or other substrates to cells. Specific DNA sequences are designed and synthesized in a laboratory to target specific cells. Modified viruses are an excellent vector to deliver these sequences because viruses can enter cells, including hard-to-reach specific cells. Using viral vectors for gene therapy makes it possible to modify gene expression by programming the cells with targeted genetic material.

Upstream bioprocessing for gene therapy typically uses transient or stable transfection to produce viral vectors. Both methods have advantages and disadvantages, so selecting the optimal vector manufacturing process for the specific dose and patient population is important.

The difference between gene and cell therapy is that gene therapy involves using a carrier, or vector, to transfer genetic material. The genetic material is inserted into the genome of targeted cells in the body.

In comparison, cell therapy involves introducing or injecting cells that function as desired into the patient's body. Cells may come from the patient (autologous cells) or a donor (allogeneic cells) and are expanded and/or modified before injecting them. Genetic modification, for example to produce CAR T-cell therapies or a modified stem cell therapy, can be achieved using viral vectors, mRNA or gene editing technologies like CRIPSR.Both gene and cell therapies improve body functions, but only gene therapy alters the patient's cellular genetics.

Another difference between gene and cell therapy is in bioprocessing. Gene therapy can be easier to manufacture at larger scales when compared to cell therapy. One reason is that gene therapy upstream bioprocessing is comparable to recombinant manufacturing. Cell therapy bioprocessing remains manual and requires customization that limits its manufacturing capacities.