The Era of Gene Editing

The advances made in genetic engineering and gene editing in recent times have been many and amazing. Improvements to the CRISPR/Cas 9 gene editing method have allowed easy, accurate, and targeted modifications to human DNA.

Likewise, the development of a method to grow tissue-specific organoids (kinds of 'mini-organs') could help in modeling diseases, screening drugs, and possibly even replacing defective tissue.

What if we can combine these two?

Scientists are currently developing methods to bring together the best of both technologies, allowing them to grow organoid not only from naturally-occurring cells, but also from gene edited cells.

See the video below to learn more about how CRISPR works:

New Efforts

One such scientist working on these methods is Hans Clevers, of Utrecht University in the Netherlands. He is using adult gut stem cells, which are the only ones that get constantly renewed, in his technique. Ultimately, this allows him to directly grow organoids from patient tissue, without having to first convert the cells to induced Pluripotent Stem Cells (iPSC).

In his 2013 study regarding cystic fibrosis, a condition caused by a gene defect that leads to thick mucus buildup in the pulmonary and gastrointestinal tract, Clevers was able to show the combination of these two technologies.

Now, there's been a new breakthrough.

A substance called forskolin has different effects to organoids grown from healthy tissue and those cultured from tissue infected with cystic fibrosis. The problem is that healthy tissue organoids swell when exposed to forskolin, while there is no effect of infected organoids. The researchers then edited the genetic defect away using CRISPR/Cas9 and homologous recombination, and then used these cells to grow organoids. When subjected to forskolin, the genetically-modified organoids swelled up like healthy tissue would.

Clever's techniques are not limited to simple genetic diseases. In 2015, his team used CRISPR to manipulate genes linked to colon cancer, and then used the resulting cells to grow organoids. When transplanted into mice, these organoids grew the tumors characteristic of invasive carcinoma.

But Clever's work is not the only ones in the field.  Sara Howden of the Murdoch Childrens Research Institute in Australia is using CRISPR to develop kidney organoid models, while University of Washington’s Benjamin Freedman has developed a way to grow kidney organoids, which are used to study diseases like polycystic kidney disease (PKD).

It is truly a new age in fighting disease, and the future is looking remarkably bright.

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