Base editing & CRISPR

A nine-month-old boy, Kyle “KJ” Muldoon Jr, has become the first known person to receive a customised gene-editing treatment using base editing, a powerful new form of genetic therapy, according to a May 15 report in the New England Journal of Medicine.

What Was the Problem?

• KJ was born with a rare genetic disorder called CPS1 deficiency.
• This condition causes toxic ammonia build-up in the blood, which can be fatal or cause severe brain damage.

What Was the Treatment?

• Researchers from the University of Pennsylvania and Children’s Hospital of Philadelphia used a tailor-made treatment based on “base editing”, a safer, more precise version of the CRISPR-Cas9 gene-editing technology.

What Is CRISPR-Cas9?

• Originally discovered in bacteria, CRISPR is a genetic immune system used to fight viruses.
• When a virus infects the bacterium:
  • The bacterium stores part of the virus’s DNA.
  • Later, it uses this DNA to create a “guide RNA”, which finds the matching virus DNA during a new infection.
  • Then the Cas9 enzyme acts as molecular scissors, cutting the virus DNA.
• In 2012, Doudna and Charpentier replicated this system in labs to create CRISPR-Cas9, earning them a Nobel Prize in Chemistry in 2020.

What Is Base Editing and How Is It Different?

• CRISPR-Cas9 makes double-strand breaks in DNA — like cutting both rails of a ladder.
• Base editing, on the other hand:
  • Does not break both strands.
  • Edits a single base pair with high precision using a Cas9 enzyme fused to a base-modifying enzyme.
• DNA consists of four chemical bases: A (adenine), T (thymine), C (cytosine), and G (guanine).
• Example: If a mutation causes a C to be where a T should be, base editing can directly change C to T, correcting the genetic error without major damage.

Why It Matters:

• KJ’s case is a historic first — a custom gene-editing treatment made just for one individual, showing the potential for personalized genetic cures.
• It offers hope for treating rare genetic diseases where traditional drugs or therapies fail.
• This success opens new doors in precision medicine and safe gene editing for previously untreatable conditions.

(Source: IE)