To know how genetic therapy works, you need to have a basic knowledge of the anatomy and how a cell functions. In this section, we give a very brief intro to human cell biology, providing enough background so that the anyone can understand how it works. It is our aim to attempt to dispel any possible misconceptions that interested parties may have about genetic therapy, and to introduce the topic to those interested in pursuing further education in this area.

The Human Body

The human body is comprised of multiple different organs that each have a given role in maintaining the good health of an individual. The brain controls our thought and reasoning; the heart pumps blood around our body supplying all the organs with essential nourishment; the lungs oxygenate our blood thus supplying the energy we need to function; the stomach, kidneys, liver, intestine and bladder all function in unison to extract nutrients from our food and dispose of unwanted toxins. Each organ plays an vital and unique part keeping us alive. genee

In order to carry out its appointed role, an organ consists of billions of cells of discrete types, each arranged in tightly controlled structures that form the overall architecture of the organ. It is the cells that are in fact responsible for the appropriate functioning of the organ. If an organ is misfunctioningn, then in order to treat it, we must fix the cells.

Basic Cell Biology

Most cells are made up of similar components: a nucleus, contains the genetic blueprint; a variety of organelles, small elements that carry out processes such as energy production, much like the way that different organs carry out specific functions of the body (e.g. lysosome, mitochondrion, golgi etc); the cytoplasm, the liquid medium that comprises the cell, and the plasma membrane, the structure that surrounds the cell and maintains its shape.

In many ways, it is the nucleus that is the most important organelle of a cell, in that it contains all the information necessary to produce each constituent of the cell. Each organelle and cellular makeup is made up of protein, sugars and lipids (fatty compounds), and the nucleus not only encodes for the synthesis of each of these components, but also the contains the instructions for their correct assemblage and final location. This information is contained within the cell’s DNA, which is the major consituent of the nucleus and is tightly condensed in a highly organised manner in the nuclear membrane.

THe Nucleus

In the interior the nucleus our DNA is arranged into 23 sets of chromosomes (or 22 pairs, and one X chromosome and Y chromosome if you are a man). These 46 chromosomes are together known as the human genome, as they contain each gene that acts as the blueprint of the human body. We can imagine of our DNA as a long straight molecule that is split into 46 separate units (i.e. the chromosomes). Inside each chromosome there are tens of thousands of genes lined up consecutively one after another, and separated by intergenic regions. Each gene is a unit of DNA that encodes for a specific protein, with a exclusive function. It is the mixture of many different proteins, and their actions on different molecules like sugars and lipids, that make up the basis of the organelle, and therefore, of the cell itself. stylowakobieta

So one can imagine that in a pathological situation, where an organ is malfunctioning, we can time and again trace the malfunction to a faulty protein that is not performing its allocated task. These protein malfunctions can either be genetic, or acquired in the course of (1) an infection, (2) a faulty immune response to one’s own cells, (3) untimely tissue degeneration, or (4) the generation of a cancer. So, in any circumstance where a disease, of any type, can be traced to a dysfunctional protein, or where a protein of known activity can restore the proper functioning of a cell, gene therapy can be used. This is simply because we can instantly use the proper gene to convey the correct type of the protein to the cell we want to repair. It is important to note that by delivering genes specifically into unhealthy cells, there is very little opportunity of passing this new genetic information in the future to our children. To do this, the our germ cells would have to be the target for gene transfer, a process that is illegal.

Application of Genetic Therapy

Effective gene transfer into human cells is known to be the biggest challenge in Gene Therapy. A gene transfer agent has to be safe, introduce its DNA cargo into a sufficiently large amount of cells to create a biological response and mediate transcription of the desired gene for a sustained duration. Identifying a vector that meets all of these criteria has proven to be a testing task.

Gene Therapy is generally used in diseases where the cells of a distinct organ or system cannot function correctly due to the fact that they do not have the correct protein that is essential to perform a desired task. In order to replace the malfunctioning protein, a gene transfer vector (such as a disabled adeno associated virus) is altered so that it contains the gene that encodes for this protein. The modified vector is then given to the patient where it enters the non-functional cells. The vector then transfers the therapeutic gene to the cell and the cell’s own machinery turns the therapeutic gene into correct version of the protein, which in essence fixes the malfunctioning cell.