Question

1. The following questions concern Jesse Gelsinger who suffered from partial OTC.

            a. In the United States the average person eats far more protein than needed to meet the demands of protein synthesis in their cells. What happens to the extra amino acids? Be specific.

            b. Describe Jesse’s illness.

            c. Briefly describe the experimental treatment he underwent.

Answer 1

a) The excess amino acids enter the urea cycle in order to b excreted from the body through the urine. Amino acids cannot just quit the body, they need to be transformed into urea and then urea is excreted

b) This illnes is the ornithine transcarbamylase deficiency, this enzyme is crucial for the correct function of the urea cycle pathway, it is allows the convertion of ornithine into citrulline. If this enzyme fails then nitrogen residues start to accumulate in the toxic molecule known as ammonia. This disease is acquired due to a mutated form of the gene that produces a nonfunctional enzyme, it is inherited in an X linked recessive manner

c) He underwent a gene therapy delivered by viral vectors. The functional copy of the gene is inserted into the vector genome, the vector is then inyected in the body for it to go and infect the cells, the has the sequences needed to insert its genome but cannot replicate and kill the cells, so it was expected to insert the correct gene for it to be normally expressed from that moment an on. The expression of this functional gene would have compensated Jesse's deficiency.

The therapy in that moment was underdeveloped and even when the principles were good Jesse died a few days afeter due to a strong immune response in his body agains the viral vectors.