Delivering gene therapy directly to the fetus of a pregnant mother is something that biotechnology futurists have dreamed about since the late 1990s. A year ago, however, the idea started moving from science fiction to reality when a British study revealed that pregnant women would be open to the possibility of becoming test subjects for research aimed at using gene therapy to treat what’s called severe early-onset fetal growth restriction (FGR). Whether clinical research proceeds in the United Kingdom or somewhere else, biotechnology is moving in a direction that can only encourage a push for fetal gene therapy research in the years to come. The main biotechnology advance at center stage is called CRISPR, pronounced “crisper”, and we’ll talk about later in this post and more so in other posts. First though, here’s some perspective on why we’re even talking about gene therapy in a blog about pregnancy.
Severe FGR is rare and the odds are that you’ll never have to worry about it. But there are many different genetic disorders, affecting newborns with a varying degree of severity. As time goes on, there are more and more conditions that can be pinned down to one or a few genes. Many of these conditions are pretty rare, but adding them together you see that having some kind of rare genetic condition is fairly common. Thus, an increasing number of mothers in the years to come will be learning early that their expected babies have one genetic disease or another. As this knowledge grows, however, more options will become available for intervening and intervention could include fetal gene therapy.
So what does gene therapy even mean? At present, gene therapy refers to treatments in adults and children that add genes to specific body cells. Soon, it may also include treatments that delete particular genes from body cells. By “body cells” (also called somatic cells), I mean cells that comprise various tissues in the body, but not gametes, the reproductive cells: eggs in women and sperm in men. Since gene therapy avoids a patient’s gametes, it has no effect on the patient’s future children and grand children or any of their descendants. But it can change the patient’s life. Gene therapy is working well, for instance, for correcting a blood disease called hemophilia B. It is also curing certain diseases, the liver, and other organs, and the list keeps growing.
Delivering a gene to an organ, or to a fetus, requires a carrier vehicle, such as a virus. The virus that works best is called AAV, but it has limited carrying capacity, kind of like a Volkswagen Beetle. Only small genes can be delivered through the body, but some genetic diseases result from problems with large genes. Here’s where CRISPR comes in, because it’s basically an editing system. Just as you can cut and paste words in a document on computer program, CRISPR enables researchers to edit an organism’s genome –its collection of genetic information. With CRISPR, gene therapists will be able to line-item edit small parts of a gene, for instance the gene that’s defective in a disease called Duchenne Muscular Dystrophy (DMD). The CRISPR machinery, plus the small amount of genetic material needed, not to replace, but merely repair, the defective DMD gene, can fit inside an AAV virus. This means that CRISPR can bring gene therapy to the next level and this certainly would apply to any gene therapy administered to a fetus.