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1. General Principles & Basic Science MCQs

Practice Set 28 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 541

Topic: 1. General Principles & Basic Science

When designing a plasmid vector for gene delivery to mesenchymal stem cells, an antibiotic resistance gene is typically included. What is the primary purpose of this specific gene?

. To prevent bacterial infection of the cell culture
. To promote integration of the plasmid into the host genome
. To serve as a selectable marker to identify successfully transfected cells
. To increase the transcription rate of the therapeutic gene
. To facilitate entry of the plasmid across the cell membrane

Correct Answer & Explanation

. To serve as a selectable marker to identify successfully transfected cells

Explanation

Antibiotic resistance genes in plasmids act as selectable markers. When the cell population is exposed to the antibiotic, only the cells that successfully took up the plasmid survive, allowing for their isolation.

Question 542

Topic: 1. General Principles & Basic Science



The image represents basic viral integration. The occurrence of leukemia in some early gene therapy trials using retroviral vectors was primarily attributed to which of the following mechanisms?

. Severe immunologic reaction to the viral capsid
. Insertional mutagenesis activating an oncogene
. Contamination of the viral vector with wild-type virus
. Toxicity from the high expression of the therapeutic gene
. Depletion of essential host transcription factors

Correct Answer & Explanation

. Insertional mutagenesis activating an oncogene

Explanation

Retroviruses integrate semi-randomly into the host genome. In early trials, this integration occurred near proto-oncogenes (insertional mutagenesis), inadvertently activating them and leading to clonal expansion and leukemia.

Question 543

Topic: 1. General Principles & Basic Science



This image illustrates a physical method of introducing DNA into cells using short, high-voltage electrical pulses. This technique is known as:

. Lipofection
. Microinjection
. Electroporation
. Sonoporation
. Biolistics (Gene gun)

Correct Answer & Explanation

. Electroporation

Explanation

Electroporation uses brief, high-voltage electrical pulses to create transient pores in the cell membrane, allowing naked DNA to enter the cell. It is an effective non-viral, physical method of gene transfer.

Question 544

Topic: 1. General Principles & Basic Science

Which viral vector integrates its genetic material into the host cell genome, carrying a risk of insertional mutagenesis?

. Adenovirus
. Adeno-associated virus
. Retrovirus
. Herpes simplex virus

Correct Answer & Explanation

. Retrovirus

Explanation

Retroviruses integrate into the host genome, providing stable long-term expression but with a risk of insertional mutagenesis. Adenoviruses remain episomal.

Question 545

Topic: 1. General Principles & Basic Science

In orthopedic gene therapy, what is the primary advantage of ex vivo gene transfer compared to in vivo transfer?

. Lower cost and complexity
. Reduced risk of systemic immune response to the vector
. Higher efficiency of targeted in vivo cell transfection
. Eliminates the need for cell culture

Correct Answer & Explanation

. Reduced risk of systemic immune response to the vector

Explanation

Ex vivo gene therapy involves harvesting cells, transducing them in vitro, and implanting them back. This reduces the systemic immune response to the viral vector compared to direct in vivo injection.

Question 546

Topic: 1. General Principles & Basic Science

Adeno-associated viruses (AAV) are frequently used in orthopedic research for gene delivery. Which of the following is a primary characteristic of AAV?

. High immunogenicity
. Integrates randomly into the host genome at high frequency
. Requires a helper virus for replication
. Large packaging capacity (>30 kb)

Correct Answer & Explanation

. Requires a helper virus for replication

Explanation

AAV is a parvovirus that requires a helper virus (like adenovirus) to replicate. It has low immunogenicity and a relatively small packaging capacity (~4.7 kb).

Question 547

Topic: 1. General Principles & Basic Science

Which non-viral method of gene transfer utilizes lipid bilayers to encapsulate plasmid DNA for delivery into cells?

. Electroporation
. Gene gun
. Lipofection
. Microinjection

Correct Answer & Explanation

. Lipofection

Explanation

Lipofection uses liposomes (lipid vesicles) to encapsulate DNA, allowing it to merge with the cell membrane and deliver genetic material. This method typically has very low immunogenicity compared to viral vectors.

Question 548

Topic: Biology, Genetics & Bone Healing

A researcher is evaluating the expression of BMP-2 protein levels in a harvested osteoblast culture following gene transduction. Which laboratory technique is most appropriate for quantifying specific protein levels?

. Southern blot
. Northern blot
. Western blot
. Polymerase chain reaction (PCR)

Correct Answer & Explanation

. Western blot

Explanation

Western blotting is used to detect and quantify specific proteins in a sample using antibodies. Southern blotting detects DNA, while Northern blotting detects RNA.

Question 549

Topic: 1. General Principles & Basic Science

What is the primary function of RNA interference (RNAi) using small interfering RNA (siRNA) in orthopedic molecular biology?

. To permanently alter the genomic DNA sequence
. To promote transcription of target genes
. To selectively silence target gene expression at the mRNA level
. To enhance ribosomal assembly

Correct Answer & Explanation

. To selectively silence target gene expression at the mRNA level

Explanation

siRNA binds to specific messenger RNA (mRNA) molecules, leading to their degradation. This effectively silences the expression of the target gene post-transcriptionally.

Question 550

Topic: 1. General Principles & Basic Science

When designing an in vivo gene therapy strategy for bone healing using a plasmid vector, what is the most significant limitation compared to viral vectors?

. Higher cost of production
. Increased risk of insertional oncogenesis
. Severe systemic immune response
. Lower transfection efficiency

Correct Answer & Explanation

. Lower transfection efficiency

Explanation

Plasmid (non-viral) vectors are safer and less immunogenic than viral vectors but suffer from significantly lower transfection efficiency. Their gene expression is also typically transient.

Question 551

Topic: 1. General Principles & Basic Science

In the context of cartilage repair gene therapy, transferring the gene for Interleukin-1 Receptor Antagonist (IL-1Ra) aims to:

. Increase matrix metalloproteinase (MMP) production
. Stimulate chondrocyte apoptosis
. Block the catabolic effects of IL-1 on chondrocytes
. Promote osteophyte formation

Correct Answer & Explanation

. Block the catabolic effects of IL-1 on chondrocytes

Explanation

IL-1 is a potent catabolic cytokine in osteoarthritis that upregulates degrading enzymes. Overexpressing IL-1Ra competitively inhibits IL-1, reducing cartilage degradation and MMP production.

Question 552

Topic: 1. General Principles & Basic Science

Which viral vector is characterized by remaining episomal within the host nucleus, having a high transient transduction efficiency, but carrying a high risk of evoking an immune response?

. Lentivirus
. Adenovirus
. Retrovirus
. Adeno-associated virus

Correct Answer & Explanation

. Adenovirus

Explanation

Adenoviruses do not integrate into the genome, thus remaining episomal, and provide high but transient gene expression. However, they are highly immunogenic, which limits their repeated use in vivo.

Question 553

Topic: 1. General Principles & Basic Science

A laboratory utilizes a technique that separates DNA fragments by size using an electrical field. This technique is known as:

. Flow cytometry
. Gel electrophoresis
. Mass spectrometry
. Microarray analysis

Correct Answer & Explanation

. Gel electrophoresis

Explanation

Gel electrophoresis uses an electrical field to push negatively charged DNA molecules through a gel matrix. Smaller DNA fragments travel further and faster than larger ones, separating them by size.

Question 554

Topic: Biology, Genetics & Bone Healing

Lentiviruses are a subclass of retroviruses increasingly used in orthopedic gene therapy. What unique advantage do they offer over traditional retroviruses?

. They do not integrate into the host genome
. They are strictly non-immunogenic
. They can transduce both dividing and non-dividing cells
. They have a strict tropism for osteoblasts only

Correct Answer & Explanation

. They can transduce both dividing and non-dividing cells

Explanation

Unlike standard retroviruses which require cells to be actively dividing to enter the nucleus, lentiviruses can transport their genome into the nucleus of non-dividing cells. This broadens their applicability in tissues like cartilage.

Question 555

Topic: 1. General Principles & Basic Science
In the CRISPR-Cas9 gene editing system, what component provides the targeting specificity to direct the Cas9 nuclease to the exact genomic location?
. Trans-activating crRNA (tracrRNA)
. Guide RNA (gRNA)
. Protospacer adjacent motif (PAM)
. Homology-directed repair (HDR) template

Correct Answer & Explanation

. Guide RNA (gRNA)

Explanation

The guide RNA (gRNA) is designed to be complementary to the specific target DNA sequence. It guides the Cas9 enzyme to the correct locus to create a double-strand break.

Question 556

Topic: Biology, Genetics & Bone Healing

Gene therapy utilizing the delivery of the BMP-2 gene to muscle-derived stem cells has been shown to induce heterotopic ossification. What type of cellular process primarily characterizes this new bone formation?

. Endochondral ossification
. Intramembranous ossification
. Apoptosis
. Dedifferentiation

Correct Answer & Explanation

. Endochondral ossification

Explanation

Muscle-derived stem cells transduced with BMP-2 typically undergo a cartilage intermediate phase followed by osteogenesis. This process mimics endochondral ossification to form ectopic bone.

Question 557

Topic: 1. General Principles & Basic Science

Plasmids are frequently used as non-viral vectors in basic science orthopedic research. What best describes the structure of a typical plasmid?

. A single-stranded RNA virus
. A small, circular, double-stranded DNA molecule distinct from chromosomal DNA
. A lipid vesicle used to deliver proteins
. A structural protein found in bacterial cell walls

Correct Answer & Explanation

. A small, circular, double-stranded DNA molecule distinct from chromosomal DNA

Explanation

Plasmids are extrachromosomal, circular, double-stranded DNA molecules found naturally in bacteria. They can replicate independently and are easily engineered to carry therapeutic genes of interest.

Question 558

Topic: Biology, Genetics & Bone Healing

When utilizing ex vivo gene therapy for delayed fracture healing, what is the most common and practical target cell harvested, genetically modified, and re-implanted?

. Erythrocytes
. Mesenchymal stem cells (MSCs)
. Mature osteocytes
. Polymorphonuclear leukocytes

Correct Answer & Explanation

. Mesenchymal stem cells (MSCs)

Explanation

Mesenchymal stem cells (MSCs) are ideal vehicles for ex vivo gene therapy in orthopedics. They are easily harvested from bone marrow, expandable in culture, and possess osteogenic potential.

Question 559

Topic: Biology, Genetics & Bone Healing

Which of the following growth factors, commonly targeted in fracture healing gene therapy, functions as a powerful factor primarily stimulating the formation of new blood vessels?

. BMP-7
. TGF-beta 1
. VEGF
. IGF-1

Correct Answer & Explanation

. VEGF

Explanation

Vascular Endothelial Growth Factor (VEGF) is a primary driver of angiogenesis. This is a critical step in the early phases of fracture healing and endochondral ossification.

Question 560

Topic: 1. General Principles & Basic Science

Microarrays are powerful tools increasingly utilized in orthopedic molecular biology. What are they primarily used for?

. Sequencing an entire organism's genome
. Simultaneously measuring the expression levels of thousands of genes
. Creating recombinant viral vectors
. Direct visualization of protein-protein interactions

Correct Answer & Explanation

. Simultaneously measuring the expression levels of thousands of genes

Explanation

DNA microarrays allow researchers to analyze the global gene expression profile by measuring thousands of mRNA transcripts simultaneously. They are often used to compare normal versus diseased tissue, such as OA cartilage.

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