Genome Editing is now at its Prime — New Prime Editing Technology

There is a new genome editing technology that allows us to search, and replace genetic codes in DNA strands, ultimately curing genetic conditions/diseases and saving lives. This technology is called prime editing but before we talk about this, we need some background knowledge that will serve to to help us understand this technology.

The human blueprint (DNA)

  • adenine (A)
  • guanine (G)
  • cytosine (C)
  • thymine (T)

These letters that are read from the DNA represents the genome code of lifeform. These codes are copied into RNA (single strand of smaller version of DNA) and passed onto ribosome to create essential proteins.

This whole process creates a perfectly shaped protein.The letters of the chemicals in the RNA tell the ribosome what type of amino acid to add to the chain.

CRISPR

  1. Guide RNA (gRNA) — (has the information of where to cut)
  2. Cas9 (protein that’s going to do the cutting)

Once the exact location of the gene that needs to be edited is identified by gRNA, the Cas9 which is an enzyme produced by the CRISPR system binds to the DNA to cut it at that point. Cas9 makes a double cut, which then triggers the DNA to repair the cut or allows for the correct genetic code to be inserted. CRISPR technology is used for the following:

  • Disable a gene (which can be achieved easily)
  • May fix a mistake (error in gene) or insert a new gene (an extremely difficult process)

As exciting as this technology may be, there are evidences that prove double stranded breaks in the DNA are not completely safe.

Prime Editing

Prime editing is similar to CRISPR, however, instead of cutting the double helix in the DNA, it is programmed to search for a desired strand and edit it. Scientists have found this safer, and more efficient. This technology can accurately insert or delete a section of the DNA and also change/correct a single nitrogenous base out of the three billion that make up human genetic code. Prime Editing is made up of the following three components:

  • Cas9 enzyme which acts like a molecular scissors. This however only cuts one strand of DNA as apposed to two.
  • Reverse transcriptase which read the RNA, uses the RNA as a template and creates DNA which is complementary to the RNA strand.
  • The PEG RNA (Prime Editing Guide RNA) acts as a navigator, navigating the complex (a group of two or more polypeptide chains) to the target DNA in the genome. It is different from other guide RNAs because it attaches to both sides of the DNA for more stability.

The PEG RNA forms a complex with the cas9 enzyme and the reverse transcriptase. Once bonded together, the complex is brought to the target sequence through the PEG RNA so the Cas9 enzyme can cut one strand.

The PEG RNA has two distinct pieces.

  • the complementary sequence which binds to the target gene of the DNA (acts as the binding region).
  • the RNA sequence which codes for the new edit (acts as the editing region)

The reverse transcriptase then reads the RNA sequence on the PEG RNA, then it reverse transcribes the corresponding nucleotides or letters of the sequence to create a DNA sequence which is the same as the previous strand of DNA except for the small area of the desired edit. This new sequence is then placed where the DNA was cut.

Once the DNA with the targeted change is integrated, there may be a mismatch between the changed DNA and the original DNA (which may not allow the changed DNA strand to be accepted by the cells). To overcome this problem, the non-edited strand is nicked (to create an illusion of damage), to trick the system so that edited strand is not altered by the cell.

Essentially, prime editing is a tool used for precise gene editing without using donor DNAs (eliminating various undesirable mutations within the genome).

Is Prime Editing important?

David Liu of the Broad Institute of MIT and Harvard and postdoctoral fellow Dr. Andrew Anzalone, say that Prime Editing technology has the potential to correct 89% of known disease-causing genetic variations in DNA. Prime editing is going to help in the research of bio-engineering field to create major breakthroughs. Also, Prime editing can be used in the agriculture sector to increase the yield by genetically modifying the crops’ DNA. This will be a huge step forward to tackle famine around the world.

What does the future hold for Prime Editing?

15 y/o AI/ML Developer | Currently diving into the neurotech space | 🥯🚚