Gene Therapy 2.0: New Method Could Dramatically Increase Efficiency

A new technique involving something called a mini-intronic plasmid (MIP) can significantly enhance expression of a transgene delivered through gene therapy

Gene therapy is extremely expensive, and researchers have been attempting to improve efficiency for some time. Making every ounce of therapy more effective could reduce cost and boost efficacy too. In its common form, gene therapy involves delivery of a strand of DNA packaged inside a modified virus. This virus finds and essentially injects this DNA template into cells across the body on in a specific tissue, and your body then transcribes that DNA into proteins. This usually either replaces a faulty copy of a gene, blocks 'bad' gene expression, or adds extra copies of a beneficial one. 

The problem with this technique is that it's often fairly weak, and researchers have been working on ways of increasing the amount of protein produced from the newly delivered transgene. A transgene is a foreign gene delivered into an organism from another source (whether synthetically modified or extracted from another organism). 

Boosting efficiency

The gene you want to deliver is included in a circular plasmid carried within your viral delivery system. This plasmid is a circular DNA strand, with a number of important components. 

A team working on this efficiency problem have now developed an alternative. In order to package up a particular transgene, it must be included in something called a plasmid. This is a circle of DNA that includes the transgene and important signals that trigger the cells to begin transcribing RNA from the DNA code. It also includes a range of other important features that must be present for the structure to work correctly.

The researchers found that by shortening some of this, and placing a number of these essential bacterial components within a region of the plasmid called an intron - they could boost transcription by up to 40 and 100 fold. An intron is a section of DNA that is non-coding, meaning it isn't transcribed as a protein. For a reason that isn't entirely understood yet, including this intronic element within a mini plasmid they called a mini-intronic plasmid (MIP), enabled far higher gene expression. If this technique is proven to work, it could reduce manufacturing costs and seriously boost gene therapy's effectiveness. Reducing the dosage is a good thing in avoiding immune complications too. 

"Careful observation of the expression characteristics of different vector designs sometimes leads to unexpected findings. In this case, the authors found that a very substantial increase in the amount of transgene expression (up to 100-fold) could be achieved from rAAV vectors by including essential bacterial plasmid elements in an upstream intron. This could present substantial advantages for future in vivo gene therapy."

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