Molecular biology and genetics: antisense therapy in spinal muscular atrophy: practice question

A Biochemistry question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Biochemistry · Molecular biology and genetics: antisense therapy in spinal muscular atrophy

Sample item

An infant with hypotonia and tongue fasciculations is found to have a homozygous deletion of SMN1. Intrathecal nusinersen, an antisense oligonucleotide, is started. How does it work?

AIt delivers a working SMN1 copy into motor neurons using a viral vectorBIt promotes exon 7 inclusion in SMN2 transcripts, raising functional SMN proteinCIt blocks ribosome binding to SMN2 mRNA to prevent toxic protein synthesisDIt triggers RNase H cleavage of the mutant SMN1 transcript before translation occurs

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

B. It promotes exon 7 inclusion in SMN2 transcripts, raising functional SMN protein

SMN2 differs from SMN1 by a base change that causes most transcripts to skip exon 7, giving an unstable protein. Nusinersen binds an intronic splicing silencer and promotes exon 7 inclusion, so SMN2 produces more full-length functional SMN protein. Gene therapy with an SMN1-carrying vector is a separate approach.

Option by option

A. It delivers a working SMN1 copy into motor neurons using a viral vector
Viral vector delivery of SMN1 describes onasemnogene, a different therapy.
B. It promotes exon 7 inclusion in SMN2 transcripts, raising functional SMN protein (correct)
Correct. The oligonucleotide corrects splicing of SMN2 to include exon 7.
C. It blocks ribosome binding to SMN2 mRNA to prevent toxic protein synthesis
It increases SMN protein; blocking translation would worsen the disease.
D. It triggers RNase H cleavage of the mutant SMN1 transcript before translation occurs
RNase H degradation of a mutant transcript is not the mechanism, and SMN1 is deleted here.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is B, It promotes exon 7 inclusion in SMN2 transcripts, raising functional SMN protein. SMN2 differs from SMN1 by a base change that causes most transcripts to skip exon 7, giving an unstable protein.

Why is "It delivers a working SMN1 copy into motor neurons using a viral vect…" not the answer?

Viral vector delivery of SMN1 describes onasemnogene, a different therapy.

Why is "It blocks ribosome binding to SMN2 mRNA to prevent toxic protein synt…" not the answer?

It increases SMN protein; blocking translation would worsen the disease.

Why is "It triggers RNase H cleavage of the mutant SMN1 transcript before tra…" not the answer?

RNase H degradation of a mutant transcript is not the mechanism, and SMN1 is deleted here.

What concept does this question test?

It tests Molecular biology and genetics: antisense therapy in spinal muscular atrophy in Biochemistry. Nusinersen binds an intronic splicing silencer and promotes exon 7 inclusion, so SMN2 produces more full-length functional SMN protein. Gene therapy with an SMN1-carrying vector is a separate approach.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Molecular biology and genetics: antisense therapy in spinal muscular atrophy?

Build one table of enzyme deficiency, disease, inheritance and key finding, then revise it by spaced recall. Then use the flashcards and the other Biochemistry questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.