Brain Primer

Modifying Genes as a Form of Therapy

  • Reviewed22 Dec 2023
  • Author Knvul Sheikh
  • Source BrainFacts/SfN
Gene therapy thumbnail via koto_feja

Genes provide the blueprint for creating every living entity on Earth. Comprised of DNA, our genes contain the information we need to develop and mature.

When genes contain flawed or mutated instructions, the organism may fail to develop properly or result in various disorders that may impact our lives. Physicians and scientists have been working to create treatment options to cure these problems by rewriting our genetic blueprints via gene therapy.

Gene therapy seeks to replace mutated genes with good copies in an effort to prevent, treat, or cure a disease or disorder. They work by adding or altering a person’s missing or mutated genes with a corrected version. A wide range of conditions can be treated with gene therapy, including both genetic diseases and disorders you are born with or those that develop as you age.

Neuroscientists are finding new ways to deliver therapeutic genes into cells that need them. For example, small viruses with healthy genes tucked inside can cross the blood-brain barrier and replace faulty genes. Currently, adeno-associated viruses and lentivirus seem to be the safest and most efficient vectors for gene therapy. These vectors are being used in clinical trials in patients with Parkinson’s disease and for some rare genetic diseases. Herpes simplex virus and adenovirus vectors have also been evaluated in early-stage human trials for treating brain tumors.

Another technique called CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) rewrites the script for “conventional” gene therapy. The genome editing technology uses RNA-guided enzymes to snip or add DNA segments to a cell, allowing researchers to make extremely precise changes to a cell’s genome. Neuroscientists have deployed CRISPR in a variety of ways. One study used CRISPR to repair part of a gene that produces toxic protein aggregates in the brains of mouse models of Huntington’s disease. When scientists looked at the mouse brains a few weeks after the procedure, the aggregated proteins typical of Huntington’s were almost gone, and the animals’ motor abilities had improved.

Genes are your body’s blueprints. Though genes contain all the information your body needs to build and maintain itself, sometimes genes contain flawed instructions. Editing these mutated genes requires rewriting the blueprints. CRISPR-Cas9, or CRISPR for short, lets scientists do just that.

The usefulness of gene-editing technologies goes beyond direct therapeutic applications. With CRISPR, dozens of animal models can be made much more efficiently, better facilitating studies of the brain and mental illness. But the technology is still relatively new, and it’s not perfect. The CRISPR system can make unintended cuts in the DNA if sequences are similar enough, resulting in unforeseen mutations that can lead to health consequences. In addition, this technology is not yet useful for treating complex conditions thought to involve multiple genes like schizophrenia.

The ethics for using CRISPR for humans remain under debate. In 2018, a genetics researcher attempted to genetically modify embryos to protect twin children from inheriting the human immunodeficiency virus, or HIV. The news sparked global debates on the bioethical use of CRISPR in humans — namely CRISPR genome editing of germ cells, or cells that produce eggs or sperm. *In December 2023, the U.S. Food and Drug Administration (FDA) approved its first cell-based gene therapy using CRISPR for the treatment of sickle cell disease. As research using CRISPR continues, people will determine the ethical intricacies of using gene therapies in the human brain.

*This article was updated December 12, 2023 to include information on the U.S. FDA's first approved CRISPR therapy, aimed at treating sickle cell disease.

Adapted from the 8th edition of Brain Facts by Knvul Sheikh.



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