Gene therapy basics Practice Questions
21 free Gene therapy basics practice questions for the USMLE Step 1. Tap an option to answer — you get instant feedback, the correct answer, and a detailed explanation for every question.
What is the primary goal of gene therapy?
- A To change a person’s diet to reduce disease risk
- B To modify a person’s genes to treat or cure a disease
- C To transplant diseased cells into a healthy donor
- D To use antibodies to neutralize pathogens
Correct answer: To modify a person’s genes to treat or cure a disease
Gene therapy aims to modify a person's genes — adding, replacing, or editing genetic material — to treat or cure disease. This distinguishes it from dietary, transplant, or antibody-based approaches.
Which of the following is the most common type of delivery vector used in gene therapy?
- A Bacterial plasmids delivered orally
- B Engineered viruses (viral vectors)
- C Synthetic small molecules
- D Direct injection of proteins
Correct answer: Engineered viruses (viral vectors)
Engineered viruses (viral vectors) are the most common delivery method because they efficiently carry genetic material into human cells, exploiting a virus's natural ability to enter host cells.
Which of the following describes an “in vivo” gene therapy approach?
- A Gene is modified in cultured cells, then transplanted back into the patient
- B Genetic material is delivered directly into the patient’s body
- C Only animal studies are done
- D Gene therapy applied to bacterial infections
Correct answer: Genetic material is delivered directly into the patient’s body
In vivo gene therapy delivers the therapeutic genetic material directly into the patient's body to transduce target cells in place, unlike ex vivo approaches that modify cells outside the body first.
Which strategy describes “ex vivo” gene therapy?
- A Injecting naked plasmid DNA straight into the bloodstream
- B Delivering a viral vector to target tissue inside the patient
- C Modifying the patient's own cells in culture, then re-infusing them
- D Administering small interfering RNA (siRNA) by mouth
Correct answer: Modifying the patient's own cells in culture, then re-infusing them
Ex vivo gene therapy removes the patient's cells (e.g. stem or immune cells), modifies them in culture by gene addition or editing, and re-infuses them. It is used in some blood disorders and cancers.
Which viral vector type is particularly favored for gene therapy because it typically does not integrate into the host genome, reducing risk of insertional mutagenesis?
- A Adeno-associated virus (AAV)
- B Lentivirus
- C Retrovirus
- D Herpes simplex virus
Correct answer: Adeno-associated virus (AAV)
AAV is favored because its genome stays largely episomal (non-integrated) in target cells, lowering the risk of disrupting host genes and causing insertional mutagenesis compared with integrating vectors like retroviruses and lentiviruses.
What is one major limitation of AAV vectors in gene therapy?
- A They always integrate into the host cell's DNA
- B Large genes exceed their small packaging capacity
- C They frequently cause severe immunodeficiency
- D They cannot transduce non-dividing cells at all
Correct answer: Large genes exceed their small packaging capacity
AAV vectors have a small packaging capacity (~4.7 kb), so large therapeutic genes plus their regulatory elements often cannot fit. AAV is mostly non-integrating and can transduce non-dividing cells, so the other options are false.
Which of the following is a potential benefit of gene editing (e.g., using CRISPR) over traditional gene addition therapy?
- A It avoids all immune detection by using no delivery vector
- B It corrects the mutation directly at its native gene locus
- C It works only in non-human experimental cells
- D Its effects are always fully reversible afterward
Correct answer: It corrects the mutation directly at its native gene locus
Gene editing (e.g. CRISPR) can correct or disrupt a mutation directly at its native locus, restoring normal gene function and regulation, rather than adding a separate working copy as in traditional gene-addition therapy.
What is a major concern associated with genome-editing gene therapy methods like CRISPR in clinical application?
- A Poor ability of the editing machinery to enter target cells
- B Off-target edits causing unintended mutations elsewhere
- C Inability to correct any disease-causing mutation
- D It always triggers immune rejection of edited cells
Correct answer: Off-target edits causing unintended mutations elsewhere
A major risk of CRISPR and other nucleases is off-target editing — unintended DNA breaks or mutations elsewhere in the genome — which is a critical safety concern in therapeutic gene editing.
Which of the following is NOT a major type of gene therapy approach?
- A Gene addition (supplying a functional gene)
- B Gene silencing or knockdown
- C Gene editing/correction
- D Gene vaccination via live attenuated virus
Correct answer: Gene vaccination via live attenuated virus
The main gene therapy strategies are adding a functional gene, silencing a harmful gene, or editing a defective gene. Using a live attenuated virus for vaccination is not a gene therapy approach.
Why is tissue-specific targeting an important consideration when designing gene therapy vectors?
- A To ensure the vector infects only bacteria, not human cells
- B To maximize therapeutic expression in target cells, sparing others
- C Because vectors can only survive within the target tissue
- D Because non-target tissues contain no DNA to modify
Correct answer: To maximize therapeutic expression in target cells, sparing others
Tissue-specific targeting delivers the therapeutic gene mainly to diseased cells, raising efficacy and reducing off-target toxicity in other tissues. Vector tropism and promoter choice are key to achieving this specificity.
Which of the following is a non-viral method of gene delivery in gene therapy?
- A Adenoviral vector
- B Lentiviral vector
- C Cationic liposome (lipoplex)
- D Adeno-associated virus (AAV)
Correct answer: Cationic liposome (lipoplex)
Non-viral delivery methods include cationic liposomes (lipoplexes), electroporation, and gene guns, which introduce DNA without viral vectors, though generally at lower efficiency.
What is the difference between gene therapy and traditional drug therapy?
- A Gene therapy alters the patient's genes; drugs act via external molecules
- B Gene therapy is always reversible, unlike conventional drug therapy
- C Drug therapy edits DNA directly, whereas gene therapy uses proteins
- D The two are essentially identical in their mechanism of action
Correct answer: Gene therapy alters the patient's genes; drugs act via external molecules
Gene therapy works at the genetic level — adding or altering genes in the patient's cells — whereas traditional drug therapy uses chemicals that modulate cellular processes without changing the genome.
Which of the following diseases would be most amenable to gene therapy using ex vivo modification of hematopoietic stem cells?
- A Retinal dystrophy affecting photoreceptor cells
- B Spinal muscular atrophy affecting motor neurons
- C Inherited blood disorders such as β-thalassemia
- D Osteoarthritis of the weight-bearing joints
Correct answer: Inherited blood disorders such as β-thalassemia
Inherited blood disorders are well suited to ex vivo gene therapy: hematopoietic stem cells are removed, genetically corrected in culture, and reinfused to restore normal blood cell production.
What is one ethical concern unique to germline gene therapy (modifying sperm, eggs, or embryos) as opposed to somatic cell gene therapy?
- A The risk of immediate immune rejection of the edited cells
- B Genetic changes can be passed on to future generations
- C The generally lower efficiency of gene delivery to embryos
- D An inability to correct the underlying disease-causing mutation
Correct answer: Genetic changes can be passed on to future generations
Germline gene therapy could permanently alter the human germline, passing changes to future generations and raising ethical concerns about consent, long-term effects, and societal impact.
Which regulatory challenge is commonly associated with clinical application of gene therapy?
- A Standard dosing of small molecules
- B Need for long-term safety monitoring over years
- C Lack of any immune response risk
- D Ease of reversing the therapy if side-effects occur
Correct answer: Need for long-term safety monitoring over years
Because gene therapy can permanently change cells, long-term follow-up is needed to detect delayed adverse effects such as insertional mutagenesis or immunogenicity, making post-treatment surveillance critical.
Which of the following best describes why a “perfect vector” for gene therapy does not yet exist?
- A Because no known virus is able to enter human cells
- B Because every vector trades off efficiency, capacity, targeting, and safety
- C Because non-viral methods always integrate genes into host DNA
- D Because current vectors work only in laboratory animals
Correct answer: Because every vector trades off efficiency, capacity, targeting, and safety
Every delivery vector has trade-offs — viral vectors may integrate unpredictably or provoke immune responses, while non-viral methods may be inefficient or poorly targeted — so no single vector is universally optimal.
How can gene therapy address diseases caused by a dominant negative mutation (where a mutant gene product interferes with normal function)?
- A By adding another copy of the normal gene without touching the mutant
- B By silencing or knocking down the mutant allele's expression
- C By ignoring the mutant allele, since such mutations self-correct
- D By delivering the gene exclusively through non-viral vectors
Correct answer: By silencing or knocking down the mutant allele's expression
In dominant-negative disorders, silencing the mutant allele (e.g. via RNA interference or gene disruption) suppresses the harmful product's interference with normal function — an established gene therapy approach.
Which statement about non-viral gene delivery systems is correct compared to viral vectors?
- A They always integrate the therapeutic gene into the host genome
- B They typically achieve higher transduction efficiency than viruses
- C They are less immunogenic but often less efficient and transient
- D They self-replicate inside the cell just like viral vectors do
Correct answer: They are less immunogenic but often less efficient and transient
Non-viral methods (e.g. liposomes, electroporation) avoid viral immunogenicity and insertional mutagenesis, but their delivery efficiency is usually lower and expression often transient, limiting effectiveness.
Which gene therapy approach could potentially treat a recessive loss-of-function genetic disease by restoring missing protein function?
- A Gene silencing of a dominant mutant allele in the cell
- B Adding a functional copy of the defective gene
- C Germline deletion of every copy of the gene
- D Overexpression of a non-coding regulatory RNA
Correct answer: Adding a functional copy of the defective gene
In loss-of-function recessive disorders, adding a correct functional copy of the gene restores protein production and corrects disease — a classic gene-addition application.
Which of the following is an advantage of using in vivo gene therapy over ex vivo gene therapy?
- A It completely avoids any immune response in all cases
- B It can reach hard-to-harvest tissues such as neurons
- C It still requires cell culture and later reinfusion
- D It is fully and easily reversible after treatment
Correct answer: It can reach hard-to-harvest tissues such as neurons
In vivo gene therapy delivers genetic material directly to target tissues in the body, which is advantageous for cells that are hard to harvest (e.g. neurons, muscle) and avoids cell removal and reinfusion.
Why is immune response a major concern in gene therapy using viral vectors?
- A Because viral vectors are unable to enter human cells
- B Because pre-existing immunity may neutralize the vector or cause inflammation
- C Because the immune response actually boosts gene expression
- D Because immune reactions never occur with viral vectors
Correct answer: Because pre-existing immunity may neutralize the vector or cause inflammation
The immune system may recognize viral vectors as foreign and neutralize them or mount inflammatory responses, reducing efficacy and raising safety concerns — a key challenge in clinical gene therapy.