Genetically Engineered Therapies: Curing the Kidney’s Related Illness

Despite of the lethality, kidney diseases affect many people today and the effects are significant. Kidney diseases include kidney stones, cyst on kidney, kidney failure and even kidney cancer. Common medical treatments employ many things including chemotherapy for cancer and hemodialysis for kidney malfunction. But, recent medical breakthrough suggested us to cure the diseases through gene therapy so that the kidneys perform cells regeneration.

There are so many diseases related to kidney and they are employed several treatments. But, when a person is suspected for kidney failure or cancer, many people would think transplantations, hemodialysis and chemotherapy are the best solutions. Because kidneys are one of the important organs which employ essential biological activities, we must find the best solution in term of sustainability medical treatment. Even though, transplantations and hemodialysis are classified as the best solution but they are not cheap and depends on the availability of organ donors and require a life-long use of immunosuppresive drugs.

Genetically Engineered Therapies: Curing the Kidney’s Related Illness

Biologically speaking, organs transplantations can result in injection from the patient's body. Otherwise, it is the same thing like we inject an alien matter to our body and the body will commence the immune system. On the other hand, hemodialysis demands high expenses and it must be performed frequently. Consequently, many people only survive for short duration of times. Interestingly, Manoe J. Janssen of the University of Utrecht presented a paper which reviewed the new method of kidney regeneration in in vivo condition.

How the therapies can be performed?

This paper proposed that gene based therapies can be used to correct abnormal processes in the cell that lead to kidney disease. These include damage due to reduced oxygen, scaring and fibrosis due to increased inflammation, but also abnormal cell function due to genetic mutations. Since the kidneys are influenced by those factors, they will not be able to perform their normal biological process. To prevent cell death and eventually kidney failure, DNA or RNA sequences can be used as a therapy to promote kidney regeneration and help the kidney to remain functional.

At some point the cells in the body will decide the damage and they can kill themselves -- auto-killing term of apoptosis --, this is an understandable biological mechanism. These processes are controlled by specific DNA and RNA sequences that control the faith of the cells. Adding a short DNA sequence to the cells with a new instruction can help the cell to become healthy again. In case of a genetic disease, there is a mistake in the DNA of the cell. Researchers can now design specific proteins which can precisely correct these mistakes (CRISPR/Cas9). By re-engineering the specific gene in RNA sequence, this paper suggested that the body will replace a missing gene which can trigger permanently repairation or regeneration and prevent further damage to the kidneys. And this medical treatment is popular as the name of gene based therapies.

Since, the gene will be engineered throughout slicing the specific gene, understanding the affected gene sequence is essential. In term of biological mechanisms, we need to identify the gene very thoroughly. For instance, in conducting the anti-cancer gene therapies, scientists must modify the genome which can commence apoptosis so it can regenerate themselves. But, every method will find challenges also. In this paper, they mentioned several clinical experiments which have been set up and there are four groups of diseases influenced by this method including the cancer diseases. The others are monogenetic and infectious, and cardiovascular diseases which address different challenges including restoring cell function, decreasing the risk of inflammation respectively.

Gene Delivering Methods

Every DNA sequence performs a different function and in case of the gene therapies, those must be delivered to the cell. Subsequently, after slicing those must be carried by transporter which the scientists called as promotor. This promotor operates together with the engineered gene and the promotor will decide if the process can be started or not. Depending on the therapy, it may be better that only specific cells will perform the instructions on the DNA.  In that case a promotor sequence that is only activated in a specific cell type will be used. As a result, the transgene procedure will actively induce in specific part of the organs – which is the kidneys – because these cells can recognize it. Because we need to perform inside the human’s specific cell, it must be employed with a certain signal.

The principle begins by introducing the recombinant protein inside the cells. It must be transferred through lipophilic membrane because it is the place for cell in performing the DNA sequence. However, the awareness must be considered since the transfer process is influenced by four aspects which are the efficiency of transduction, the duration of transferring, and toxicity and body’s immune response and the size of the DNA. Otherwise, it can be rejected by the body so that the scientists need to pack the DNA.

There are many advantages and disadvantages for every used packaging system. Either naked DNA or non-viral vectors, such as synthetic and natural compounds packaged with the naked DNA, have limitation in the efficiency of the amount. Even though, they are less toxicity so the human’s body will accept them. While, the virus which is mostly functioned as the transporter or vector triggers the immune system and the size of the engineered DNA is limited because virus is very small. So, the carrier must be biocompatible and efficient when it arrives inside the cell.

Based on those understanding, the scientists suggested that the Extracellular vesicles is the best package for delivering the gene. It is small and can attach molecules including miRNA, mRNA, lipids, proteins, and the DNA which is from the vesicles itself. The vesicles are exosomes and microvesicles which can be employed by horizontal transfer of RNA or intravenous injection. Based on this paper, there are many research which have been employing this method either to animals or human’s tissue.

Conclusion

The gene-based therapy through extracellular vesicles which is reviewed by Manoe J. Janssen et al., is one of the best safety method in kidney treatment. It is a biocompatible even though it is not clinically employed. Nevertheless, this therapy demonstrate that the kidney failure can be regenerated automatically even though it is not 100 percent fully-recovered. Furthermore, this method can be considered as a potential method which can prevent further effects of kidney diseases.

*Manoe J. Janssen, Fanny O. Arcolino, Perry Schoor, Robert Jan Kok, Enrico Mastrobattista. 2016. Gene Based Therapies for Kidney Regeneration. European Journal of Pharmacology 790 (2016) 99-108.