Duchenne muscular dystrophy (DMD) is caused by mutations in

the dystrophin gene that often introduce frame shifts, resulting in the absence

of functional dystrophin and severe muscle degeneration. In contrast,

individuals with Becker muscular dystrophy produce a shorter but partially

functional dystrophin protein and experience a milder disease phenotype.

Antisense oligonucleotide therapies have been developed to

shift the DMD phenotype toward a Becker-like outcome. Which mechanism best

explains how antisense oligonucleotides achieve this effect?

To minimise unintended genome damage, a gene-editing

strategy must ensure that nuclease activity is restricted to a single,

predefined genomic site. In zinc finger nuclease–based approaches, this

specificity is achieved through a modular DNA-binding architecture.

Which component of a ZFN construct is primarily responsible

for recognising and binding the target DNA sequence?

A gene therapy is being developed to permanently inactivate

a dominant gain-of-function mutation that causes a severe neurological

disorder. The therapeutic strategy involves introducing a targeted

double-strand break within the mutant gene, without providing a repair

template.

Which DNA repair pathway is being deliberately exploited in

this therapeutic design, and why?

A long-term follow-up study of patients treated with a viral

vector–based therapy for a genetic brain disorder shows stable expression of

the therapeutic protein years after treatment. Importantly, there is no

evidence of insertional mutagenesis, abnormal cell proliferation, or disruption

of endogenous gene regulation.

Which feature of the viral vector most plausibly explains

both the durability and safety of this therapeutic outcome?

A new antidepressant is undergoing clinical development. At

one stage, the study is designed to determine whether the drug is safe and well

tolerated.

Which study feature is most essential at this stage of

development?

The following information is relevant to this question:

Approximate volumes of body compartments

• Plasma volume                           ~0.05 L/kg
• Total extracellular volume           ~0.2 L/kg
• Total body water                         ~0.55 L/kg

The Vd of a drug is determined to be 0.09 L/kg.  Based on this information, which of the following statements is MOST consistent with this Vd?  The drug is:

A pharmaceutical company is preparing a first-in-human

clinical trial for a new small-molecule drug. Before selecting a safe starting

dose for healthy volunteers, the compound is administered to animals in a

single-dose, acute pre-clinical toxicity study to assess immediate adverse

effects.

Which piece of information from this study would be most

relevant for guiding the choice of the initial human dose?

EL-07 is an active drug and metabolised by CYP2C19.  26% of the population are classified as CYP2C19 poor metabolisers.

In these patients, the standard dose of EL-07 is likely to result in:

During the COVID-19 pandemic, several vaccines were

developed and made available to the public in record time. Despite the usual

lengthy process for vaccine development, these vaccines completed pre-clinical

and clinical testing, and received regulatory approval much faster than

typical.

Which factor most plausibly explains how this accelerated

development was achieved?

During lead optimisation, all lead compounds were evaluated using the forced swim test in mice. 

Table 2: Assessment of in vivo efficacy of lead compounds in rodents

In the forced swim test, decreased immobility is considered to be associated with antidepressant activity 

Values given as mean ± SEM

Based upon the data shown in Table 2, which of the compounds is MOST LIKELY to be effective in the treatment of patients with severe depression?