Gene Therapy

NCERT grounding

Section 10.2.2 of NCERT Class XII Biology, titled Gene Therapy, opens with a single defining sentence and then commits the rest of the section to one canonical case. The definition is reproduced almost verbatim on the NEET paper every two or three years, so it is worth treating as fixed text rather than paraphrase.

"Gene therapy is a collection of methods that allows correction of a gene defect that has been diagnosed in a child/embryo. Here genes are inserted into a person's cells and tissues to treat a disease. Correction of a genetic defect involves delivery of a normal gene into the individual or embryo to take over the function of and compensate for the non-functional gene."

The chapter then introduces the historical anchor — the first clinical gene therapy of 1990, given to a 4-year-old girl with adenosine deaminase (ADA) deficiency — and lays out the experimental steps that NEET 2018, 2021 and 2022 have all sampled from. The end-of-chapter exercise (Question 8) asks students to illustrate gene therapy using the example of ADA deficiency, which essentially scripts the question pattern the entrance paper imitates.

What gene therapy actually does

Most diseases that NEET students meet — diabetes, tuberculosis, malaria — are treated by adding a drug, a hormone or a microbe-killing molecule from outside the patient's cell. Gene therapy is different in kind. It does not supply a missing protein from outside; it supplies the missing instruction for making that protein. The drug, in effect, is a piece of DNA. Once installed in the patient's cell, the cell's own ribosomes manufacture the functional enzyme from then on.

This shift of layer matters in two ways. First, it explains why gene therapy is a candidate cure for hereditary single-gene disorders in particular: such disorders are caused not by an outside agent but by a defective version of a gene present in every cell of the patient from birth. Adding back a functional copy directly attacks the cause. Second, it explains why gene therapy is technically harder than ordinary drug therapy: the corrective agent (the gene) must reach the right cells, cross the plasma membrane, evade host nucleases, integrate into or persist alongside the host genome, and continue to be transcribed at appropriate levels for as long as the patient needs it.

NCERT's working definition collapses these requirements into a single phrase: delivery of a normal gene into the individual or embryo to take over the function of and compensate for the non-functional gene. NEET 2021 (Q.116) tested this definition against three close cousins — biopiracy, molecular diagnosis and safety testing — and the trap students fall into is choosing molecular diagnosis when the stem says "gene targeting" or "gene amplification". The phrase gene targeting involving gene amplification sits inside the NCERT supplement that the 2021 paper drew from, and the only correct answer there is gene therapy.

Why ADA deficiency was the chosen case

Adenosine deaminase is one enzyme in the purine salvage pathway. Without it, deoxyadenosine accumulates inside developing lymphocytes and kills them. The patient is left with no functional T-cells, no proper B-cell maturation, and a complete failure of acquired immunity — severe combined immunodeficiency. Untreated SCID children classically die of opportunistic infection within the first year of life.

Three properties made ADA deficiency the natural first case for gene therapy. The disorder is caused by deletion of a single, well-characterised gene, so there is a clear corrective payload. The affected cell type — the lymphocyte — is easy to harvest from blood and easy to return through the same vein. And ADA expression does not need delicate timing or huge protein quantities; even modest restoration of enzyme activity rescues lymphocyte survival.

The 1990 ADA case — step by step

The 1990 protocol is the only worked example NCERT gives, and the NEET paper tests its sequence directly. The five steps below are the canonical version reproduced in every modern edition of the chapter.

Two design choices in this protocol carry almost all of the NEET marks. The first is the use of cDNA rather than the genomic ADA gene. cDNA — complementary DNA copied from mature mRNA by reverse transcriptase — already lacks introns, so it is short enough to fit inside a retroviral vector and the host lymphocyte can express it without splicing. The second is the choice of a retroviral vector. Retroviruses reverse-transcribe their RNA genome inside the host cell and integrate the resulting DNA into a host chromosome. Integration is what makes the corrected gene heritable to the daughter cells of that lymphocyte — but only for as long as that lymphocyte and its descendants stay alive.

This last clause is the hinge on which NEET 2022 (Q.166) turns. The stem asks why the patient requires periodic infusion. The trap options list every true statement about the procedure — lymphocytes are grown in culture, a retroviral vector is used, marrow cells could in principle be transduced at the embryonic stage — but only one of those statements is the reason behind the periodic infusion. The reason is that genetically engineered lymphocytes are not immortal cells. They die off; the ADA activity goes with them; the patient comes back for another batch.

Somatic vs germline therapy

Every gene therapy procedure must answer one prior question: which cells of the patient get the corrected gene? The answer splits the field cleanly into two categories that NEET tests as an explicit pair.

For NEET purposes, three points settle most questions. Somatic therapy is the default; it is what the 1990 case was; it is what is meant when the paper says simply "gene therapy" with no qualifier. Germline therapy is the route that would make the cure permanent for that family lineage. And the bridge between the two is the bone marrow stem cell: introducing ADA cDNA into a haematopoietic stem cell rather than a mature lymphocyte means every daughter lymphocyte the patient ever produces carries the corrected gene — a permanent cure in the patient, without going as far as altering gametes.

Ex vivo vs in vivo delivery

A second axis cuts gene therapy by where the gene transfer happens — inside the body or outside it. NCERT does not name this distinction explicitly, but it is unavoidable in NEET extensions of the topic.

Vectors and the CRISPR-Cas9 era

Whichever route is used, the corrective gene has to be carried by a vector. NEET focuses on one — the retrovirus — because that is what NCERT names in the ADA case and what the paper has tested directly. But a one-line awareness of the modern landscape is useful, because it explains why gene therapy has moved from a single 1990 case study to an approved class of medicines.

Retroviral vectors

A retrovirus carries a single-stranded RNA genome. Once inside the host, viral reverse transcriptase copies that RNA into double-stranded DNA, which then integrates into a host chromosome via the viral integrase. For gene therapy, the pathogenic genes are removed from the viral genome and replaced by the corrective human gene (here, ADA cDNA). The engineered virus retains its ability to enter cells and integrate, but cannot replicate or cause disease. NEET 2018 (Q.112) tested this directly — the vector used to introduce a DNA fragment into human lymphocytes is a retrovirus, not Ti plasmid, not λ phage, not pBR322. (Ti plasmid is for plants; λ phage and pBR322 are bacterial cloning vectors.)

CRISPR-Cas9 and modern editing

The retroviral approach adds a working copy of the gene but does not repair the broken one. Modern editing tools — most famously the CRISPR-Cas9 system — go a step further: a guide RNA directs the Cas9 nuclease to the exact defective sequence in the genome, where it makes a precise cut, and the cell's own repair machinery is harnessed to splice in a corrected sequence. CRISPR is not part of the NCERT Class XII chapter and has not yet appeared on a NEET paper, but it underlies most contemporary clinical gene therapies and is the natural follow-on to the 1990 retroviral protocol that NCERT describes.

Worked examples

Common confusion & NEET traps