A gene that is inserted into a cell directly usually does not function. Thus, a carrier molecule called a vector can be used to deliver the therapeutic gene to the patient’s target cells. Currently, the most common vector is a virus genetically altered to carry normal human DNA. Viruses have evolved a way of encapsulating and delivering their genes to human cells in a pathogenic manner. Scientists have tried to take advantage of this capability and manipulate the virus genome to remove disease-causing genes and insert therapeutic genes.
Target cells such as the patient’s liver or lung cells would be infected with the viral vector. The vector then unloads its genetic material containing the therapeutic human gene into the target cell. The generation of a functional protein product from the therapeutic gene restores the target cell to a normal state.
These are some of the different types of viruses used as gene therapy vectors:
- Retroviruses– A class of viruses that can create double-stranded DNA copies of their RNA genomes. These copies of its genome can be integrated into the chromosomes of host cells. Human immunodeficiency virus (HIV) is a retrovirus.
- Adenoviruses– A class of viruses with double-stranded DNA genomes that cause respiratory, intestinal, and eye infections in humans. The virus that causes the common cold is an adenovirus.
- Adeno-associated viruses– A class of small, single-stranded DNA viruses that can insert their genetic material at a specific site on chromosome 19.
- Herpes simplex viruses – A class of double-stranded DNA viruses that infect a particular cell type, neurons. Herpes simplex virus type 1 is a common human pathogen that causes cold sores.
Besides virus-mediated gene-delivery systems, there are several nonviral options for gene delivery:
- The simplest method is the direct introduction of therapeutic DNA into target cells. This approach is limited in its application because it can be used only with certain tissues and requires large amounts of DNA.
- Creation of an artificial lipid sphere with an aqueous core. This liposome, which carries the therapeutic DNA, is capable of passing the DNA through the target cell’s membrane.
- By chemically linking the DNA to a molecule that will bind to special cell receptors, the therapeutic DNA are engulfed by the cell membrane and passed into the interior of the target cell. This delivery system tends to be less effective than other options.
- Researchers also are experimenting with the introduction of a 47th (artificial human) chromosome to target cells. This chromosome would exist autonomously alongside the standard 46 without affecting their functions or causing any mutations. It would be a large vector capable of carrying substantial amounts of genetic code, and scientists anticipate that, because of its autonomy, the body’s immune systems would not attack it. A problem with this potential method is the difficulty in delivering such a large molecule to the nucleus of a target cell.
The researchers must also ensure that the genes are fully controlled by the body after being inserted.
A new gene is injected into an adenovirus vector, which is used to introduce the modified DNA into a human cell. If the treatment is successful, the new gene will make a functional protein.