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1. General Principles & Basic Science MCQs

Practice Set 27 of 789

This practice set contains high-yield board review questions covering key concepts in 1. General Principles & Basic Science. Each clinical scenario is designed to test your diagnostic and management skills relevant to this subspecialty.

Question 521

Topic: 1. General Principles & Basic Science

All of the following have been used as viral vectors for gene delivery except:

. Adeno-associated virus
. Rotavirus
. Herpes simplex virus
. Lentivirus
. Retroviral vector

Correct Answer & Explanation

. Lentivirus

Explanation

A retroviral vector derived from the Moloney murine leukemia retrovirus is among the best-developed viral vectors. Other viral vectors include adenovirus, adeno-associated virus, and herpes simplex virus. Novel vector systems based on lentivirus, a type of retrovirus, which includes human immunodeficiency virus (HIV), are being developed.

Question 522

Topic: 1. General Principles & Basic Science

The principle of homologous recombination in gene therapy is used to:

. Replace a defective gene by a wild-type gene
. Suppress the expression of a mutant gene
. Supplement a wild-type gene
. Alter the expression of a mutant gene
. Replacement of a defective gene by a normal gene

Correct Answer & Explanation

. Replace a defective gene by a wild-type gene

Explanation

Novel approaches to treating genetic diseases involve gene repair or replacement rather than gene supplementation. One such approach is based on homologous recombination (replacement of a defective gene by a normal gene).

Question 523

Topic: 1. General Principles & Basic Science
The virus associated with most immune reactions is:
. Adeno-associated virus
. Gutted adenovirus
. Adenovirus
. Retrovirus
. Herpes simplex virus

Correct Answer & Explanation

. Adenovirus

Explanation

Adenoviral vectors can cause inflammatory reaction due to immune activation, an event linked to the first death related to gene therapy. This occurred in September 1999 at the University of Pennsylvania in a clinical trial in which an 18-year-old patient received infusion of over a trillion adenoviral vectors directed to his liver, which triggered a systemic inflammatory response that became uncontrollable, leading to organ failure and death. Newer generation gutted or gutless adenovirus vectors are nonimmunogenic.

Question 524

Topic: 1. General Principles & Basic Science

Compared to ex vivo gene delivery system, the in vivo system is:

. Technically complex
. Target specific
. Safer
. Less invasive
. More invasive

Correct Answer & Explanation

. Less invasive

Explanation

Two basic strategies exist for gene delivery. Direct, or in vivo, gene therapy involves direct introduction of vectors into the body. Indirect, or ex vivo, gene therapy involves removal of target cells from the body, vector introduction by incubation of the cells in vitro, and reimplantation. The in vivo system is less invasive.

Question 525

Topic: Biology, Genetics & Bone Healing

The gene that has been studied in greatest detail for application in osteoarthritis is:

. p-53
. Interleukin (IL)-13
. Tissue inhibitors of metalloproteinases-4
. IL-Receptor antagonist
. BMP-2

Correct Answer & Explanation

. IL-Receptor antagonist

Explanation

Gene therapy has been suggested as a means of delivering sustained therapeutic levels of anti-arthritic gene products to diseased joints. Local gene delivery to the synovial tissue is preferred for osteoarthritis and other conditions affecting a few joints. It is less suited to address the extra- articular components of systemic conditions, such as rheumatoid arthritis. The gene that has been studied in greatest detail encodes the human IL-1 receptor antagonist (IL-Ra).

Question 526

Topic: Biology, Genetics & Bone Healing

The gene studied for application in osteoporosis and wear-induced osteolysis is:

. Osteoprotegerin (OPG)
. Bone morphogenetic protein (BMP)
. Transforming growth factor-b1
. LMP-1
. IL-receptor antagonist

Correct Answer & Explanation

. Osteoprotegerin (OPG)

Explanation

Various cytokines and cytokine antagonists hold promise as new therapeutic agents for osteoporosis. Baltzer et al showed that intramedullary injection of Ad-IL-1Ra gene in a murine ovariectomy model strongly reduced the loss of bone mass. Using a similar model, Bolon et al studied the effect of adenovirus-mediated transfer of osteoprotegerin, which showed more bone volume with reduced osteoclast numbers in axial and appendicular bones after 4 weeks compared to sham-operated mice.

Question 527

Topic: 1. General Principles & Basic Science

Gene transfer to a cell using viral vectors is called:

. Transduction
. Transfection
. Transformation
. C onjugation
. Augmentation

Correct Answer & Explanation

. Transduction

Explanation

In vivo gene delivery involves the direct injection of vectors containing the genes into the body with the expectation that they will reach and transduce the target cell.

Question 528

Topic: Biology, Genetics & Bone Healing

Which of the following genes has been shown to stimulate proteoglycan synthesis for prevention of disk degeneration:

. LMP-1
. BMP-7
. Decorin
. TGF-b1
. OPG

Correct Answer & Explanation

. TGF-b1

Explanation

Intervertebral disk degeneration has been associated with a progressive decrease in proteoglycan content of nucleus pulposus. The potential application of gene therapy for prevention of disk degeneration is to increase or maintain the proteoglycan content of nucleus pulposus. Thompson et al reported that addition of TGF-b1 to canine disk tissue in culture stimulated in vitro proteoglycan synthesis.

Question 529

Topic: 1. General Principles & Basic Science

Lentiviral vectors are increasingly used in orthopedic gene therapy research. Which of the following represents the primary advantage of lentiviral vectors over standard retroviral vectors?

. Inability to integrate into the host genome
. Ability to transduce non-dividing cells
. Minimal immune response compared to adeno-associated virus
. Exclusive targeting of chondrocytes
. Lack of packaging limits for inserted genetic material

Correct Answer & Explanation

. Ability to transduce non-dividing cells

Explanation

Lentiviruses are a subclass of retroviruses unique in their ability to transduce both dividing and non-dividing cells. This is highly advantageous for targeting mature, slow-dividing orthopedic tissues like articular cartilage.

Question 530

Topic: 1. General Principles & Basic Science

Adeno-associated virus (AAV) vectors are highly favored in orthopedic gene therapy for sustained expression. Which of the following is a key characteristic of AAV?

. It causes severe human pathology in its wild-type form
. It integrates randomly into the host genome at high rates
. It requires a helper virus, such as adenovirus, for replication
. It has an enormous payload capacity exceeding 30 kb
. It primarily elicits a strong cell-mediated immune response

Correct Answer & Explanation

. It requires a helper virus, such as adenovirus, for replication

Explanation

AAV is a dependent parvovirus that requires a helper virus (like adenovirus or herpesvirus) to replicate. It is non-pathogenic, elicits minimal immune response, and typically remains episomal rather than integrating.

Question 531

Topic: Biology, Genetics & Bone Healing

In designing a gene therapy construct to enhance bone formation, researchers include a specific DNA sequence located upstream of the target gene to regulate its transcription. What is this sequence called?

. Intron
. Exon
. Promoter
. Telomere
. Stop codon

Correct Answer & Explanation

. Promoter

Explanation

A promoter is a regulatory DNA sequence located upstream of a gene that binds RNA polymerase and transcription factors to initiate transcription. Tissue-specific promoters can restrict gene expression to target cells, such as osteoblasts.

Question 532

Topic: Biology, Genetics & Bone Healing

BMP-2 is delivered via an adenoviral vector to stimulate spinal fusion in an animal model. Through which intracellular signaling pathway does BMP-2 primarily exert its osteoinductive effects?

. Wnt/beta-catenin pathway
. JAK/STAT pathway
. Smad 1/5/8 pathway
. Notch signaling pathway
. Hedgehog signaling pathway

Correct Answer & Explanation

. Smad 1/5/8 pathway

Explanation

Bone morphogenetic proteins (BMPs) bind to serine/threonine kinase receptors, leading to the phosphorylation of receptor-regulated Smads (Smad 1, 5, and 8). These complex with Smad 4 to enter the nucleus and regulate transcription of osteogenic genes.

Question 533

Topic: 1. General Principles & Basic Science

A novel therapy utilizes small interfering RNA (siRNA) to treat an autosomal dominant orthopedic condition. What is the mechanism of action of siRNA?

. Directly mutating the abnormal gene at the DNA level
. Binding to the promoter to prevent transcription
. Targeting mRNA for degradation, thus preventing translation
. Binding to the abnormal protein to facilitate proteasomal degradation
. Stimulating homologous recombination of the mutant allele

Correct Answer & Explanation

. Targeting mRNA for degradation, thus preventing translation

Explanation

siRNA mediates post-transcriptional gene silencing by binding to complementary messenger RNA (mRNA) sequences. This leads to mRNA degradation, effectively preventing translation into the disease-causing protein.

Question 534

Topic: 1. General Principles & Basic Science

Ex vivo gene therapy is utilized to deliver therapeutic proteins for articular cartilage repair. Which of the following is a characteristic advantage of the ex vivo approach compared to in vivo gene delivery?

. Lower overall cost and complexity
. Avoidance of cell culture requirements
. Ability to select and expand successfully transduced cells prior to implantation
. Elimination of the need for viral vectors
. Decreased risk of donor site morbidity

Correct Answer & Explanation

. Ability to select and expand successfully transduced cells prior to implantation

Explanation

Ex vivo gene therapy involves harvesting cells, transducing them in vitro, and implanting them back into the patient. This allows for the selection and expansion of successfully genetically modified cells, ensuring high therapeutic efficacy.

Question 535

Topic: 1. General Principles & Basic Science

Retroviral vectors require the conversion of their RNA genome into DNA before integration into the host cell. Which enzyme is responsible for this critical step?

. DNA ligase
. RNA polymerase II
. Reverse transcriptase
. Endonuclease
. Helicase

Correct Answer & Explanation

. Reverse transcriptase

Explanation

Retroviruses utilize the enzyme reverse transcriptase to synthesize a complementary DNA (cDNA) strand from their RNA genome. This DNA is then integrated into the host genome via an integrase enzyme.

Question 536

Topic: 1. General Principles & Basic Science

When utilizing adenoviral vectors for gene therapy in bone healing models, researchers must account for the specific characteristics of this vector. Which of the following is true regarding adenoviral vectors?

. They provide permanent, stable integration into the host genome
. They are highly inefficient at transducing dividing cells
. They primarily exist as episomes and provide transient gene expression
. They have a very limited packaging capacity of less than 2 kb
. They do not elicit any significant immune response

Correct Answer & Explanation

. They primarily exist as episomes and provide transient gene expression

Explanation

Adenoviral vectors deliver their genetic payload to the nucleus where it remains episomal (non-integrating), resulting in high-level but transient gene expression. They are also highly immunogenic.

Question 537

Topic: 1. General Principles & Basic Science

A family presents with multiple male members affected by Duchenne muscular dystrophy (DMD). The gene responsible for DMD is located on the X chromosome. What is the chance that an affected male will pass the mutated gene to his son?

. 0%
. 25%
. 50%
. 75%
. 100%

Correct Answer & Explanation

. 0%

Explanation

DMD is an X-linked recessive disorder. A male passes his Y chromosome to his sons and his X chromosome to his daughters. Therefore, an affected male will pass the mutation to all daughters (carriers) but no sons (0%).

Question 538

Topic: 1. General Principles & Basic Science

Polymerase chain reaction (PCR) is used to amplify specific DNA sequences for diagnosing orthopedic infections. What is the sequence of temperature phases in a standard PCR cycle?

. Annealing, Denaturation, Extension
. Denaturation, Extension, Annealing
. Extension, Annealing, Denaturation
. Denaturation, Annealing, Extension
. Annealing, Extension, Denaturation

Correct Answer & Explanation

. Denaturation, Annealing, Extension

Explanation

A standard PCR cycle consists of denaturation (heating to separate strands), annealing (cooling to allow primers to bind), and extension (optimal temperature for DNA polymerase to synthesize the new strand).

Question 539

Topic: 1. General Principles & Basic Science

A researcher is evaluating the expression level of a newly discovered cartilage degrading enzyme in synovial fluid. Which of the following laboratory techniques is most appropriate to detect and quantify this specific protein?

. Southern blot
. Northern blot
. Western blot
. Polymerase chain reaction (PCR)
. In situ hybridization

Correct Answer & Explanation

. Western blot

Explanation

Western blotting uses gel electrophoresis to separate proteins by size, followed by transfer to a membrane and probing with specific antibodies. Southern blots detect DNA, and Northern blots detect RNA.

Question 540

Topic: 1. General Principles & Basic Science

During endochondral ossification, hypertrophic chondrocytes undergo programmed cell death to allow vascular invasion and bone formation. Which of the following is the key executioner enzyme group in this apoptotic process?

. Matrix metalloproteinases
. Caspases
. Cathepsins
. Alkaline phosphatases
. Hyaluronidases

Correct Answer & Explanation

. Caspases

Explanation

Caspases (cysteine-aspartic proteases) are the central executioner enzymes in apoptosis. Their activation leads to the organized cleavage of cellular proteins, resulting in programmed cell death without eliciting an inflammatory response.

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