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Base Editing – The Cancer Therapy

Context:

Scientists from United Kingdom reported success in a new cancer therapy for a type of blood cancer T-cell acute lymphoblastic leukaemia (T-ALL).

Relevance:

GS III: Science and Technology

Dimensions of the Article:

  1. What happens in this form of cancer?
  2. What is ‘base editing?’
  3. How did base-editing actually work?
  4. How effective was the treatment?

What happens in this form of cancer?

  • T-ALL affects the stem cells in the bone marrow that produce a particular kind of white blood cells (WBC) called T lymphocytes (T cells). These cells provide a person immunity by killing cells carrying infections, activating other immune cells, and regulating the immune response.
  • At least 20% of these WBC are atypical– as they accumulate in the bone marrow, they crowd out “good” WBCs and hence weaken the immune system. These unhealthy cells can also accumulate in other parts of the body like the liver, spleen and lymph nodes.
  • While found in both children and adults, T-ALL’s incidence decreases with age.
  • Chemotherapy, Bone marrow transplant and radiation therapy are typically used to treat the disease, which progresses quickly.

What is ‘base editing?’

  • The genetic code of an individual is made up of various combinations of the nucleotides adenine (A), guanine (G), cytosine (C), and thymine (T).
  • Sequences of these bases spell out genes that provide instructions on how to make the huge variety of proteins required for bodily functioning.
  • In some cases T-cells may have developed malignancy, maybe as a result of an incorrect arrangement of the bases. A technique to fix this imbalance shall result in a stronger immune system.
  • An approach that allows for the alteration of genes and the “fixing” of mistakes has captured the attention of the biomedical engineering community in the past two decades.
  • One such leading strategy has been the CRISPR-cas9 technique.

The CRISPR-cas9

  • The CRISPR-cas 9 system employs an enzyme that functions like molecular scissors to cut off and store portions of a virus’ genes, an approach that some bacteria adopt to protect themselves against viruses.
  •  A guide RNA can be used to introduce a different genetic code at the locations of incision, and it can be programmed to cut a segment of DNA at a specific position.
  • There are a various ways to make these alterations, but the CRISPR-cas9 system is thought to be the quickest and most adaptable method.
An upgrade to CRISPR-cas9
  • The CRISPR-cas9 method has been modified by David Liu of the Broad Institute in Massachusetts so that particular bases can be changed directly.
    • For example, a C can be turned into a G and a T into an A. While still a nascent technology, base editing is reportedly more effective at treating blood disorders which are caused by so-called single point mutations, or when a change in a single base pair can cause terminal disease.

How did base-editing actually work?

  • The patient (Alyssa, a 13 year old) 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, but Alyssa’s case was different.
    • Traditionally, CAR-T therapy involves adding a gene to T-cells that causes them to seek out and 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 and reintroduced to the individual.
    • The problem with such an approach (besides the expense) 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.
    • Thus, scientists have resorted 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. Thus, Alyssa received genetically modified cells that were programmed to specifically attack her cancer while leaving the rest of her body alone.
How effective was the treatment?
  • Three months after the treatment, the cancer seemed to resurface but the most recent investigations suggest no signs of it.
  • Whether the treatment has reliably and entirely fixed the immune system, remains to be established.

-Source: The Hindu, Indian Express


February 2023
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