Researchers are, all the time, toiling to find new drugs and vaccines for incurable or hard to cure diseases like Influenza and HIV. With advances in the fields of medicine, genetics and chemistry, efforts are afoot to find new futuristic drugs, vaccines and therapies with the help of state of the art technology.
The body always responds to a pathogen by way of immune system. The immune response is expressed in the form of antigens and antibodies.
The cell membranes have specific receptors for different kinds of molecules. The pathogen triggers immune response by forcing the body to secret specific proteins called antibodies against the pathogen (called antibody).It is this antigen-antibody reaction threat neutralizes the effect of pathogen on the body or pathogen itself. Phagocytes (special type of white blood corpuscles) destroy the pathogen by feeding on them (Phagocytosis).
In order to produce antibodies against a specific pathogen naturally, pathogen has to be present in the body. To protect the body against pathogens, we employ vaccination to boost the immunity. The vaccination stimulates the immune system to secret a large no. of specific antibodies which protect against the diseases. The immunity imparted by vaccination can be of two types – active and passive. In active immunity the body produces antibodies in response to dead or inactive or weakened pathogen. Such immunity is long lasting. On the other hand in passive immunity ready made antibodies are used as vaccine to provide immunity. Such immunity is short lived.
The future vaccines are trying to balance between both active and passive types of vaccines. Researchers are testing two new types of vaccines. One vaccine consists of DNA rings called plasmids the other vaccine uses a virus called adenovirus as a carrier. Both types of vaccines employ genes that encode for proteins in the pathogenic organism so that immune cells catch the attention and start responding. But the two types of vaccines plasmid vaccines and adenovirus vaccines employ different methods of delivery. Earlier results have indicated that adenovirus vaccine have scored above plasmid vaccines in providing immunity. The difference in the response lies in the mode of drug delivery.
The plasmids are rings of extrachromsomal DNA in the bacterial cells.
The genes for the one or more proteins of the pathogen against which immunity is required are added to the plasmid DNA ring with the hope that they would provoke immune reaction from the immune system. The adenoviruses are the naked icosahedral (nearly spherical) viruses having nucleocapsid and a double stranded linear DNA molecule. A nonpathogenic adenovirus is used as carrier for encoding pathogenic protein.
The DNA vaccines have many advantages over the traditional vaccination. They can be manufactured more rapidly than traditional vaccines as these do not require handling and cultivating potentially dangerous live virus.
More over DNA is stable at room temperature where as conventional vaccines need to be refrigerated, which is cause for concern during handling, storage and transportation. The immune system does not perceive the DNA of the plasmid as foreign material as all cells of the body have DNA. Technically speaking the vaccines itself as such does not invokes any immune response. It is only the protein encoded by the plasmid that would cause immune cells to respond. This also paves way for repeated use of plasmids to deliver a variety of genes without the fear of body cells developing resistance.
However new methods of vaccines delivery had to be developed to ensure entry of plasmids in to a large no of cells.
New vaccine delivery methods use transdermal patches, gene guns and biojets using pressurized air to deliver plasmids into the skin cells.
Another method is electroportation, which uses electrical impulses to temporarily open up the cell membrane,
to allow entry of plasmids into the cell. Electroportation increases the plasmid uptake by thousand folds. The plasmids carrying DNA sequences of genes have been improved by codon optimization. The DNA carries genetic information in the form of codons, each codon consists of three nucleotide bases. An amino acid is coded by a specific codon of three nucleotide bases in a specific sequence, but certain amino acids have more than one codon that codes for a specific amino acid. It has been found that cells favor certain codons more over the other codons. Thus the production of a specific protein in the cell can be optimized by choosing optimal codons.
Each protein molecule is preceded by a leader sequence which makes protein molecule more stable. Certain leader sequences initiate the secretion of a specific protein only. The final improvement has come by way of substances called adjutants. Adjutants are chemical compounds that increase antibody response to DNA vaccines, Instead of adding chemicals to the vaccine, which will create problems regarding handling, emulsification or stability, we can incorporate DNA sequence into the vaccine plasmid itself to synthesize the adjutant along with the vaccine proteins, causing a further five fold increase in the immune response.
The ability to inject genes into cells and to get these cells manufacture encoded proteins opens up new methods of treatment. Classical drugs consist of chemical molecules which have to enter the blood stream to effect core. Most of these chemical materials are excreted or neutralized before they can affect a cure. Thus they need to be administered in large doses which are most often toxic and cause unwanted toxic effects. On the other hand the beauty of the DNA drugs lies in the fact that they will be synthesized in the body in the required amount and that too at the required site, providing a side effect free more effective treatment. Another plus point is that only one injection is required to effect the treatment. Another category of treatment called DNA biological immunotherapy combines the best aspect of DNA therapy and vaccines.
Earlier trials using DNA encoded viral proteins to induce immune cells to attack tumors have shown encouraging results. IT seems that the day is not far off, when we will be able to provide faster immunity to HIV, tuberculosis, cancer and a host of other diseases including flu. However, these vaccines and therapeutics have to undergo extensive clinical testing before human use.
The body always responds to a pathogen by way of immune system. The immune response is expressed in the form of antigens and antibodies.
The cell membranes have specific receptors for different kinds of molecules. The pathogen triggers immune response by forcing the body to secret specific proteins called antibodies against the pathogen (called antibody).It is this antigen-antibody reaction threat neutralizes the effect of pathogen on the body or pathogen itself. Phagocytes (special type of white blood corpuscles) destroy the pathogen by feeding on them (Phagocytosis).In order to produce antibodies against a specific pathogen naturally, pathogen has to be present in the body. To protect the body against pathogens, we employ vaccination to boost the immunity. The vaccination stimulates the immune system to secret a large no. of specific antibodies which protect against the diseases. The immunity imparted by vaccination can be of two types – active and passive. In active immunity the body produces antibodies in response to dead or inactive or weakened pathogen. Such immunity is long lasting. On the other hand in passive immunity ready made antibodies are used as vaccine to provide immunity. Such immunity is short lived.
The future vaccines are trying to balance between both active and passive types of vaccines. Researchers are testing two new types of vaccines. One vaccine consists of DNA rings called plasmids the other vaccine uses a virus called adenovirus as a carrier. Both types of vaccines employ genes that encode for proteins in the pathogenic organism so that immune cells catch the attention and start responding. But the two types of vaccines plasmid vaccines and adenovirus vaccines employ different methods of delivery. Earlier results have indicated that adenovirus vaccine have scored above plasmid vaccines in providing immunity. The difference in the response lies in the mode of drug delivery.
The plasmids are rings of extrachromsomal DNA in the bacterial cells.
The genes for the one or more proteins of the pathogen against which immunity is required are added to the plasmid DNA ring with the hope that they would provoke immune reaction from the immune system. The adenoviruses are the naked icosahedral (nearly spherical) viruses having nucleocapsid and a double stranded linear DNA molecule. A nonpathogenic adenovirus is used as carrier for encoding pathogenic protein.The DNA vaccines have many advantages over the traditional vaccination. They can be manufactured more rapidly than traditional vaccines as these do not require handling and cultivating potentially dangerous live virus.
More over DNA is stable at room temperature where as conventional vaccines need to be refrigerated, which is cause for concern during handling, storage and transportation. The immune system does not perceive the DNA of the plasmid as foreign material as all cells of the body have DNA. Technically speaking the vaccines itself as such does not invokes any immune response. It is only the protein encoded by the plasmid that would cause immune cells to respond. This also paves way for repeated use of plasmids to deliver a variety of genes without the fear of body cells developing resistance.However new methods of vaccines delivery had to be developed to ensure entry of plasmids in to a large no of cells.
New vaccine delivery methods use transdermal patches, gene guns and biojets using pressurized air to deliver plasmids into the skin cells.
Another method is electroportation, which uses electrical impulses to temporarily open up the cell membrane,
to allow entry of plasmids into the cell. Electroportation increases the plasmid uptake by thousand folds. The plasmids carrying DNA sequences of genes have been improved by codon optimization. The DNA carries genetic information in the form of codons, each codon consists of three nucleotide bases. An amino acid is coded by a specific codon of three nucleotide bases in a specific sequence, but certain amino acids have more than one codon that codes for a specific amino acid. It has been found that cells favor certain codons more over the other codons. Thus the production of a specific protein in the cell can be optimized by choosing optimal codons.Each protein molecule is preceded by a leader sequence which makes protein molecule more stable. Certain leader sequences initiate the secretion of a specific protein only. The final improvement has come by way of substances called adjutants. Adjutants are chemical compounds that increase antibody response to DNA vaccines, Instead of adding chemicals to the vaccine, which will create problems regarding handling, emulsification or stability, we can incorporate DNA sequence into the vaccine plasmid itself to synthesize the adjutant along with the vaccine proteins, causing a further five fold increase in the immune response.
The ability to inject genes into cells and to get these cells manufacture encoded proteins opens up new methods of treatment. Classical drugs consist of chemical molecules which have to enter the blood stream to effect core. Most of these chemical materials are excreted or neutralized before they can affect a cure. Thus they need to be administered in large doses which are most often toxic and cause unwanted toxic effects. On the other hand the beauty of the DNA drugs lies in the fact that they will be synthesized in the body in the required amount and that too at the required site, providing a side effect free more effective treatment. Another plus point is that only one injection is required to effect the treatment. Another category of treatment called DNA biological immunotherapy combines the best aspect of DNA therapy and vaccines.
Earlier trials using DNA encoded viral proteins to induce immune cells to attack tumors have shown encouraging results. IT seems that the day is not far off, when we will be able to provide faster immunity to HIV, tuberculosis, cancer and a host of other diseases including flu. However, these vaccines and therapeutics have to undergo extensive clinical testing before human use.
No comments:
Post a Comment