Targeted delivery of nucleic acids: design, preparation, impact and recent advances
Targeted delivery of nucleic acids: design, preparation, impact and recent advances
Masoumehossadat Hosseini ,1,*Ali Hossein Amini,2Rana Amini,3Navid Rabiee,4
1. Department of Organic Chemistry, Shahid Beheshti University, G.C., Tehran 1983963113, Iran Soroush Mana Pharmed, Golrang Pharmaceutical Investment Co (GPI), Golrang Industrial Group (GIG), Tehran, Iran 2. Department of organic chemistry, University of Mazandaran, Babolsar, 47416-95447, Iran 3. Department of Chemistry, University of Zanjan, Zanjan (Iran) 4. Department of Chemistry, Sharif University of Technology, Tehran, Iran
Introduction: Targeted delivery approaches for transferring therapeutic agents, especially nucleic acids, to treat certain diseases, chiefly cancers, have shown a rapid rise over the past few decades. Since the administration of nucleic acids with therapeutic potential has proved a promising approach for the treatment of several human diseases and many biological applications such as gene therapy and DNA vaccines that have already been used. Thus, on the one hand, there is a growing need for further studies on nucleic acids treatment, and on the other hand, researchers' attention is focused on the conventional methods of delivering them to the target tissue.(1-4) Considering that nucleic acids such as DNA plasmids, a variety of RNAs, oligonucleotides and synthetic nucleic acids have large dimensions and negatively charged phosphate groups within their structure and also are degradable; Therefore, their transfer to target cells requires the appropriate methods like use of viral and non-viral gene transfer systems and also physical techniques which have discussed in this article in the following. Knowing that gene therapy has the potential to replace malignant or defective genes and modify gene expression. A wide range of diseases have been studied and finally treated by gene therapy, with many cancer-related diseases, genetic disorders, neurodegenerative diseases, Alzheimer's disease and autoimmune diseases being examples of these applications. (5, 6)
In the meantime, Cancer is a type of disease that is caused by numerous genetic mutations. In fact, dynamic changes in the genome and a complex network of interactions between cancer cells with different types of cells have led to cancer progression, which in turn has led to the development of tumors. It has been proven that this mechanism and process in genetic alterations that lead to a variety of diseases actually require gene therapy and sometimes it can work best to cure diseases by removing the disruption of the expression pathway of the genes involved in producing a particular protein.(7) In the last few decades, nucleic acid delivery has shown tremendous potential for treating the aforementioned acquired and inherited diseases. In the process of gene therapy, nucleic acids, which mainly contain DNA or RNA, are transferred to the target cells for gene modification and thus to the treatment of inherited or acquired diseases. (8, 9) To understand the many uses of nucleic acids in the field of treatment, it is best to first get acquainted with the types of these macromolecules. In the beginning of this article, we have investigated the types of nucleic acids and their structure. These include oligonucleotides, aptamers, plasmid DNA ( pDNA), messenger RNA( mRNA), small interfering RNA(siRNA), short hairpin RNA (shRNA) and so on. Therefore, delivery of these nucleic acids is an important strategy that represents the goal of gene therapy. Indeed, the process of delivering these nucleic acids to the target tissues and cells is that they interact with specific intermediates upon entry of the nucleic acids into the cells, which in turn leads to expression of the gene of interest or inhibition of messenger RNA ( mRNA) translation in the defective gene and finally by blocking the expression of mRNA, it prevents the production of a defective protein that causes the relevant disease.(10) As a result of this movement, it provides direct treatment and intervention in the cause of the disease. (11, 12)
Activity in the field of gene therapy and nucleic acid therapeutic application begun around since year 1980, but the first successful gene transfer in humans was approved by the National Health Association in year 1989 and eventually used in year 1990. (13) Since then, the number of clinical trials has gradually increased and has been globally approved. Due to the increasing successes and reports in this field, more attention has been paid by researchers to this area and trends have been steered.(14) There are several methods for nucleic acid transfer including viral and non-viral methods as well as physical methods for gene transfer. Most of the research used viral vectors as a gene delivery tool for transferring nucleic acids. The use of viral vectors has led to high levels of gene expression. Although a highly efficient and impressive method of viral transmission, due to the limitation of the potential contamination of viruses to other tissues, other methods have been included.(15) In this article we tried to address each of these methods.
Methods: With the passing of time and the advancement of science and technology in human life, consequently a change in human life style has created new relevant issues that have given new thought to the solution of these issues. One of the issues related to living in the modern world is the discussion of new diseases and related therapies. With this argument, new therapeutic approaches are needed to overcome these issues. Understanding what is happening inside the living cell and examining the chemistry of living cells is a pathway that helps researchers find the right response to the treatment of many diseases. So at first it is necessary to evaluate the mechanisms of disease to be the well-known and proven treatment and then be sent using the right tools to the target tissue. One of the most exciting, promising, and tremendous therapeutic approaches in light of the ongoing developments is the use of nucleic acids in the treatment of new diseases in recent decades. Thus in this article at the beginning it is necessary to discuss about nucleic acid biochemical structure and different kinds of them after that investigating their therapeutic potential and finally the methods of their delivery to target tissues have been studied.
Results: With the passing of time and the advancement of science and technology in human life, consequently a change in human life style has created new relevant issues that have given new thought to the solution of these issues. One of the issues related to living in the modern world is the discussion of new diseases and related therapies. With this argument, new therapeutic approaches are needed to overcome these issues. Understanding what is happening inside the living cell and examining the chemistry of living cells is a pathway that helps researchers find the right response to the treatment of many diseases. So at first it is necessary to evaluate the mechanisms of disease to be the well-known and proven treatment and then be sent using the right tools to the target tissue. One of the most exciting, promising, and tremendous therapeutic approaches in light of the ongoing developments is the use of nucleic acids in the treatment of new diseases in recent decades. Thus in this article at the beginning it is necessary to discuss about nucleic acid biochemical structure and different kinds of them after that investigating their therapeutic potential and finally the methods of their delivery to target tissues have been studied.
Conclusion: Considering to this present article, the first step is to understand the nucleic acid structure and to identify the pharmacological effects and to select the correct vehicle for nucleic acid transfer and their effective delivery to the target tissue. The next step was to pick out the convenient and effectual method, knowing the various pathways involved in targeted delivery of nucleic acids. Nowadays the nucleic acid delivery systems are growing dramatically and are on the rise. As discussed throughout this article, it is necessary to know that all of the above mentioned methods all have both disadvantages and merits and have been used for this purpose with respect to the target cell type and nucleic acid.