Programmable gene editing: The search for high-precision gene editing

• Author:
• Author name

  Quantumrun Foresight
• December 19, 2022

Insight summary

Gene editing has led to exciting discoveries in genetic therapies, such as potentially "fixing" cancerous and mutated cells. However, scientists are exploring better ways to target cells more accurately through naturally occurring genetic editing processes. The long-term implications of programmable gene editing could include increased genetic research funding and better tools for personalized medicine.

Programmable gene editing context

Genome editing is a powerful technique that allows scientists to make targeted changes to an organism's genetic code. This method can be achieved in several different ways, including the introduction of DNA breaks or mutations through the use of engineered sequence-specific nucleases (SSNs).

By inducing double-stranded breaks (DSBs) within a genome, scientists can use programmed SSNs to target specific sites. These DSBs are then repaired by cellular DNA mechanisms, such as non-homologous end joining (NHEJ) and homology-directed repair (HDR). While NHEJ typically results in imprecise insertions or deletions that may disrupt gene function, HDR can introduce precise changes and potentially correct genetic mutations.

The CRISPR gene editing tool is the most widely utilized in this field, involving a guide (gRNA) and the Cas9 enzyme to "cut off" problematic strands. There are several potential benefits to using this technique, including treating diseases like cancer and HIV (human immunodeficiency virus) and developing new therapies for other disorders. However, risks are also associated, such as the possibility that specific edits could introduce harmful mutations into an organism's DNA. 

In 2021, there were already 30 web-based software platforms designed to program gRNA, according to a study published in the Trends in Plant Science journal. These programs have varying levels of complexity, with some enabling scientists to upload a wide range of sequences. Additionally, some tools can determine off-target mutations.

Disruptive impact

In 2021, scientists at the Massachusetts Institute of Technology (MIT) and Harvard University discovered a new class of programmable DNA-modifying systems called OMEGAs (Obligate Mobile Element Guided Activity) that doesn't use CRISPR technology. These systems may naturally shuffle small bits of DNA throughout bacterial genomes. This discovery opens up a unique area of biology that can elevate genome editing technology from a calculated risk to a more predictable process.

These enzymes are small, making them easier to deliver to cells than bulkier enzymes, and they can be rapidly adapted for different uses. For example, CRISPR enzymes use gRNA to target and destroy viral invaders. However, by artificially generating their gRNA sequences, biologists can now direct the Cas9 enzyme guide to any desired target. The ease with which these enzymes can be programmed makes them a powerful tool for modifying DNA and suggests that researchers could use them in developing gene editing therapies. 

Another promising research direction in programmable gene editing is twin prime editing, a CRISPR-based tool developed by Harvard scientists in 2022. The new technique allows large gene-sized chunks of DNA to be manipulated in human cells without cutting the DNA double helix. Making larger edits than previously possible could enable scientists to study and treat genetic diseases resulting from the loss of gene function or complex structural mutations, such as hemophilia or Hunter syndrome.

Implications of programmable gene editing

Wider implications of programmable gene editing may include: 

• Increased funding in genetic editing research aiming to diversify the techniques used to discover more accurate and safer care methods.
• The advancement of personalized medicine through targeted genetic and disease therapies.
• Biotech firms developing better software for genetic editing automation and precision.
• Some governments increasing their funding and research in genetic editing by implementing various pilot tests in cancer therapies.
• Longer life expectancies for people born with genetic mutations.
• Novel genetic tools being repurposed to address harmful diseases and mutations in animals and plant species.

Questions to consider

• How else do you think programmable genetic editing can revolutionize healthcare?
• What can governments do to ensure these therapies are accessible to everyone?