Genetic medicines represent a significant shift in healthcare, moving beyond symptom management to address the fundamental causes of disease. These treatments interact directly with a person’s genetic material, offering the potential for lasting therapeutic effects. By targeting the body’s genetic code, genetic medicines are creating new ways to prevent and treat a wide array of conditions. This field holds promise for improving patient care.
Understanding Genetic Medicines
Genetic medicines operate by directly engaging with an individual’s genes, DNA, or RNA to prevent or treat illness. Unlike conventional pharmaceuticals that primarily alleviate symptoms, these therapies aim to correct or compensate for genetic anomalies at their source. This approach addresses underlying genetic defects rather than their downstream effects.
The principle involves modifying or manipulating gene expression within living cells. This can mean introducing new genetic material, altering existing genes, or silencing problematic ones. These interventions are designed to restore normal cellular function, produce missing proteins, or disable disease-causing pathways.
Categories of Genetic Medicines
Genetic medicines encompass several distinct approaches, each with a unique method of interacting with genetic material.
Gene therapy involves introducing, modifying, or removing genetic material within a patient’s cells to treat a disease. This often includes adding a healthy copy of a gene to compensate for a faulty or missing one.
RNA-based therapies utilize various forms of RNA molecules to influence gene expression. Messenger RNA (mRNA) therapies can instruct cells to produce specific proteins, while small interfering RNA (siRNA) and antisense oligonucleotides (ASOs) can silence or reduce the production of disease-causing proteins. These therapies modulate gene activity without permanently altering the DNA sequence.
Gene editing, exemplified by technologies like CRISPR-Cas9, allows for precise modifications to specific DNA sequences. This technique can be used to correct a mutation, insert new genetic material at a targeted location, or remove unwanted segments of DNA.
Mechanisms of Action
Genetic medicines operate through cellular processes, beginning with the delivery of therapeutic genetic material into target cells. Viral vectors, such as adeno-associated viruses (AAVs) and lentiviruses, are often engineered as delivery vehicles. Non-viral methods, including lipid nanoparticles, also facilitate gene transfer by encapsulating and delivering genetic material into cells.
Once inside the target cells, the introduced genetic material interacts with the cell’s machinery to achieve a therapeutic outcome. This can involve the new gene integrating into the host cell’s genome, allowing for long-term production of a missing protein, as seen in some gene addition therapies. Alternatively, the genetic material might remain separate from the genome, acting as a temporary template for protein production or to modulate gene expression, such as in mRNA therapies.
The therapeutic effect can stem from various interactions, including correcting a faulty gene, producing a protein that was previously absent or deficient, or silencing an overactive gene that contributes to disease. For example, in gene editing, specific enzymes are guided to a precise DNA sequence to cut and alter the genetic code, leading to the repair of a mutation or the inactivation of a problematic gene.
Therapeutic Uses of Genetic Medicines
Genetic medicines are being applied across many diseases, offering new treatment avenues. In inherited disorders, these therapies aim to correct the underlying genetic defect. For instance, onasemnogene abeparvovec-xioi (Zolgensma) is an FDA-approved gene therapy for children under two years old with spinal muscular atrophy (SMA), a severe neurodegenerative condition caused by mutations in the SMN1 gene. Another example is voretigene neparvovec-rzyl (Luxturna), approved for an inherited retinal disease that leads to blindness. Hemophilia B, a bleeding disorder, also has an approved gene therapy, Hemgenix, for adults.
Genetic medicines are also advancing in cancer treatment. Chimeric antigen receptor (CAR) T-cell therapy, such as axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah), involves extracting a patient’s T-cells, genetically modifying them to recognize and attack cancer cells, and then reinfusing them back into the patient. These therapies are approved for certain types of blood cancers, including large B-cell lymphoma and acute lymphoblastic leukemia.
Beyond inherited conditions and cancer, genetic medicines show promise for infectious diseases and other complex disorders. Some genetic vaccines utilize genetic material to prompt the body to produce antigenic proteins, stimulating an immune response against pathogens. The potential for these therapies extends to conditions like cystic fibrosis, Duchenne muscular dystrophy, and chronic infections.