BASE EDITING

• In 2021, Alyssa was diagnosed with a particular type of blood cancer.
• A month after the infusion & a subsequent bone-marrow transplant, her cancer called T-cell acute lymphoblastic leukemia went into remission.
• Bases are the language of life. Just as letters in the alphabet spell out words that carry meaning, the billions of bases in our DNA spell out the instruction manual for our body.
• With advances in genetic technology, scientists have been able to zoom into a precise part of the genetic code to alter the molecular structure of just one base, effectively changing its genetic instructions.
• A team at the Great Ormond Street Hospital managed to use base-editing to create a new type of T-cell from a healthy donor that would not attack other cells, not kill each other, survive chemotherapy & hunt down all other T-cells in Alyssa's body.
• After this therapy worked in its initial stages, Alyssa was given another bone marrow transplant to restore her immunity.

• Alyssa was diagnosed with a kind of blood cancer known as T-cell Acute Lymphoblastic Leukaemia (T-ALL).
• T-ALL affects the stem cells in the bone marrow that produce a particular kind of white blood cells called T-lymphocytes.
• These cells provide a person immunity by killing cells carrying infections, activating other immune cells, regulating the immune response.
• Atleast 20% of these WBC are atypical as they accumulate in the bone marrow, they crowd out 'good' WBCs & hence weaken the immune system.
• These unhealthy cells can accumulate in other parts of the body like the liver, spleen & lymph nodes.
• While found in both children & adults, T-ALLs incidence decreases with age.

• Typical treatment for T-ALL is similar to that of any Leukaemia-chemotherapy & stem cell/bone marrow transplant.
• Doctors will first administer multiple rounds of chemotherapy.
• This either kills the cancerous cells or stops them from further dividing.
• The exact schedule is guided by an individual's age & general health.
• If this fails & the individual is suitable, doctors will conduct bone marrow transplant.
• First the patient will undergo radiation therapy & chemotherapy that will kill the concerous cells but also wreck an individual's immunity system along with it.
• Thus, patients receive an infusion of healthy bone marrow cells that will hopefully multiply & restore immunity.
• Overall treatment for T-ALL is pretty effective, children have a survival rate of over 85% after 5 years of receiving this treatment.
• Unfortunately, Alyssa lay in the unlucky 15% of children where the treatment just did not work.

• Alyssa received a dose of healthy T-cells from a donor that would hopefully attack her cancerous cells without destroying each other.
• Known as CAR-T therapy, this principle has been around for a while.
• Traditionally, CAR-T therapy involves adding a gene to T-cells that cause them to seek out & destroy cancerous cells.
• The modified cells are known as CAR-T cells.
• First, an individual's own T-cells are removed, which are then modified & reintroduced to the individual.
• The problem with such an approach is that very often, when an individual is really sick, it is simply impossible to obtain enough healthy T-cells to create CAR-T cells.
• While donors can provide healthy T-cells to an individual, these T-cells from a foreign body are going to attack every single cell in that patient's body, making the treatment counterproductive.
• Scientists have restored to what is known as 'Base-Editing', through this technique of genetic editing, they make it possible for one donor to supply T-cells to multiple recipients, without the traditional risks associated with it.
• Alyssa received genetically modified cells that were programmed to specifically attack her cancer while leaving the rest of her body alone.