Gene Therapy and Immune System

The American Society of Gene Therapy are holding their Annual Meeting at Baltimore and have issued this press release on gene therapy applications of RNA interference. RNA interference is "a form of post-transcriptional gene silencing in which double-stranded RNA induces degradation of the homologous endogenous transcripts, mimicking the effect of the reduction, or loss, of gene activity" (Nature Reviews). You can view an animated tour through the process of RNA interference here.

One of the challenges facing the successful utilisation of gene therapy for diseases where the patient has a functioning immune system (like hemophilia) has been the human immune system itself. And this is why this latest study is encouraging. The press release explains:

A team of scientists led by Luigi Naldini, MD, PhD, and Brian D. Brown, PhD, at the San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET) in Milan have developed a way to prevent the immune system from disturbing the efforts of gene therapists.

To accomplish this, they utilized a newly uncovered network of genes regulated by molecules known as microRNAs. Over the past 5 years, research has revealed that microRNAs have a role in almost every cellular process, including those involved in the development of cancer.

MicroRNAs downregulate the expression of specific genes in cells where the gene is not needed, and thereby have an important influence over the identity of a cell.

The HSR-TIGET group reasoned that they could use this natural function of microRNA to selectively turn off the identity of their therapeutic gene in cells of the immune system and prevent the gene from being found and destroyed. The researchers injected mice with the gene containing an immune-cell microRNA target sequence, and spectacularly, the mice did not reject the gene, as previously occurred when vectors without the microRNA target sequence were used.

"The discovery of microRNAs has changed our understanding of biology," Dr. Brown noted. "Almost every week a new study comes our implicating them in some cellular process or pathology. Now we can take advantage of this information for creating therapies."

So another small step forward in our fight to mitigate the arbitrary and often tragic consequences of the natural lottery of life.

Cheers,
Colin