Gene therapy is an approach to treating genetic diseases by re-introducing a functional copy of a gene into cells to replace the mutated, disease-causing gene. To get these genes into the cells, scientists create a vector by packaging the DNA encoding the correct gene into the outer shell–called the capsid–of a virus. A vector retains the ability of the virus to enter human cells and deliver it’s genetic cargo to the nucleus. But because the viral genome has been replaced with the corrected gene, instead of making more viruses (as would be the case in a viral infection), the cell makes the corrected version of the diseased gene, in theory curing the disease.
To treat diseases of the liver using gene therapy, scientists first need to be sure that the engineered vector is able to enter liver cells and express the genetic cargo. To do this, the capsid is packaged with a genome that encodes Green Fluorescent Protein (GFP). If the vector works, liver cells will glow green. In this series of three images, two vessels in liver tissue resemble eyes, and the colored cells surrounding the vessels are expressing GFP. The vessel layout and GFP expression pattern does not have a regular pattern, so finding these mask-like shapes required both luck and an artistic eye. The hue of the GFP signal was adjusted to create the artwork, but the intensity of each cell was not adjusted. Cells nearest the “eyes” or vessels come in contact with the most vector in the bloodstream, receive the most copies of the GFP gene, and therefore have the highest color intensity. As the adjacent cells are transduced by vector, cells further away from the vessel come in contact with a lower concentration of vector and have accordingly lower color intensity. The overall number and intensity of GFP expressing cells in the liver gives a general idea of how effective a particular vector could be to treat diseases that manifest in the liver, such as hemophilia.
By Anna Maurer, a fourth year graduate student in the Biological and Biomedical Sciences Program at Harvard Medical School.