**10. Hair follicle regrowth using gene therapy**

Gene therapy aims to deliver genetic material (DNA) into the patients' cells with either a prevention or therapeutic purpose. The therapeutic effect could theoretically be obtained by replacing the mutant gene that causes the disease with a healthy gene, inactivating a mutated gene that causes an imbalance in the organism or introducing a new gene that could fight a particular disease. For the introduction of the gene, a carrier called vector is used, and it usually consists of a modified virus (retrovirus) that will not produce a disease in the organism, but will deliver the gene by integrating the genetic material into the chromosome of a particular cell. The delivery pathway may consist of a direct injection into the tissue or it can be given intravenously, to reach the blood flow [36].

As new evidence shows that 80% of the baldness is genetic, gene therapy could be the solution, although it encounters technical problems that have not been solved up to the present [69]. Most of the hair loss complains in both female and male patients are due to the presence of androgenetic alopecia, caused by hyperandrogenism and sensitivity to dihydrotestosterone (DHT). It has been noticed that people naturally lacking from birth the 5-alpha reductase enzyme (which converts the testosterone to DHT) never develop androgenetic alopecia [50].

Human scalp has DHT-resistant follicles in the occipital area, this location being used to extract the hair follicles for transplant into the vertex or to the fronto-parietal area [53]. Gene therapy may be a solution in this case, if it can trigger the hair follicles with DHT-sensitive cells and change them into DHT-resistant follicles that could regrow hair without being affected by androgen hormones [70]. Another option would consist of the ribonucleic acid (RNA) interference to block the genes responsible for hair loss. Messenger ribonucleic acid (mRNA) represents the carrier of genetic information from the DNA out of the cell nucleus into the cytoplasm, where it is translated into specific proteins, such as receptors, enzymes. Small fragments of nucleic acids, such as small interfering RNAs (siRNAs), can target a specific gene and block the production of any type of protein in a cell. In hair loss, this technology could be used in order to inhibit the androgen receptor (AR) and the 5-alpha reductase enzymes.

Up to the present, an attempt to effectively control delivery of small interfering RNA using biodegradable cationized gelatin microspheres in an animal model of disease was first performed in 2008. Researchers administered local injections of interleukin-4 and neutralizing anti-interferon-γ antibody in C3H/HeJ mice. They concluded that alopecia areata was effectively treated as the treatment suppressed CD8 T cell infiltrates around the hair follicles and repressed enhanced interferon-γ mRNA expression in alopecic skin. Also, restoration of hair shaft elongation occurred due to Th1 transcription factor T-box 21 small interfering RNAs conjugated to cationized gelatin [71]. Another recent study showed that the sonic hedgehog (*shh*) gene stimulated the hair shaft production and anagen phase in C57BL/6 mice, after being delivered with an adenovirus vector [72].

Gene therapy is currently available only in research settings. It represents a promising therapeutic option for several diseases (especially those with no cure for the moment), but this procedure needs more research and improvement that need to be considered safe and to prove its effectiveness. So far, scientists have encountered difficulties in finding proper delivery pathways of the genes to the body, targeting them to particular cells, controlling the new gene(s) and their effect after they have been inserted into the body [73].
