Practice question

Gene therapy uses nucleic acids themselves as therapeutic agents to correct aberrant cellular function. Rather than supplying recombinant proteins or small molecules, functional DNA, mRNA, antisense oligonucleotides, or siRNAs are delivered intracellularly. Vectors derived from AAV, lentivirus, adenovirus, or synthetic ionizable lipid nanoparticles shield cargo from serum nucleases and facilitate endocytosis via heparan sulfate receptors and endosomal escape. Once in the nucleus, expression cassette comprising promoter, codon-optimized open reading frame, and polyadenylation signal undergoes transcription by RNA polymerase II, mRNA processing, nuclear export via NXF1, and translation producing proteins such as adenosine deaminase, factor IX, or CFTR channel. Alternatively, siRNA loads into Argonaute within RISC to cleave pathogenic transcripts, while antisense blocks splicing. Durable episomal persistence or stable chromosomal integration ensures long-term correction, addressing monogenic disorders at molecular root rather than symptomatically managing phenotype with frequent protein replacement. This mechanistic insight guides vector optimization, dosing strategies, and clinical safety monitoring essential for translational development and regulatory evaluation.