With more intense researches taking place in gene therapy vector areas, the microbiologists have currently come upon another unique technique to treat life-threatening diseases. They have successfully started clinical trials with AAV or Adeno-associated virus that infects human beings and some other primates as well. The virus was a great breakthrough for scientists as well patients suffering from cancers and other fatal diseases as it has been found that this virus lacks pathogenicity. The AAV vector system making use of AAV has the ability to infect both passive and dividing cells. Yet the viruses do not integrate into the genome which is why it is seen to be a better alternative to retrovirus therapy.
The Adeno-associated virus is small and underdeveloped and therefore easily manipulated for gene therapy through AAV vector system. It again is more predictable as the rep and cap of the DNA of the vector has been removed and therefore easily identifiable. Better still for research success and curability is that AAV DNA is lost in the process of cell division. This means the episomal DNA cannot be replicated as and when the host DNA divides.
Specialized Gene Therapy with AAV
AAV packaging and placid system has a distinct advantage and that it quickly integrates into the target cell yet do not do so randomly and even if it did then it was with hardly any noticeable frequency. Yet the vector does need a total replacement of its genome which can be a little tricky when proper therapy is needed. This is especially so in the case with large genes are involved. Yet scientists and microbiologists are not sparing any time and giving full effort to develop a virus that has almost double capacity.
In due course of time scientists would bring out an even better AAV vector beating the newly experimented types that are an altered version of AAV. All this would surely ensure the superiority of AAV vector over lentivirus as the later integrates into the genome. This can affect the expression of trans-genes as well as the expression of the genes in other cells in the neighborhood. In sharp contrast AAV has the least immune response and therefore the best for therapy. This naturally makes it better than others as best AAV expression system till date. It is for this unique AAV expression system that currently more and more therapeutic applications are being recorded.
If you browse here you may get details on short coding sequences of viruses and easy packaging options of AAVs. Currently, scientists have identified eleven serotypes of AAVs. The most common among them and most used is the AAV2. In order to transducer specific cell this is the best vector option for molecular biologists.
Further Strides in AAV Vector Therapy
It has been seen that microbiologists have further improved the AAV through pseudo typing. It greatly improves upon the efficiency of transduction. Apart from this they have been able to alter tropism too. Microbiologists have also developed hybrids from different serotypes of AAV for in vivo applications. The success through AAV vector has been so remarkable in clinical and off-clinical trials that their development and commercialization have begun.
The AAV expression system has wide application in therapeutic areas like CAR T-cell, oncology, regenerative kind of medicines as well as immunotherapy. This has paved way for huge investment in this field by large multinational organizations. It is generally seen that both Lentiviruses as well as AAV are used for therapeutic applications.
In sharp contrast to RNA genome of Lentiviruses, AAV has DNA genome that is single stranded. It must be noted that AAV is not derived from a pathogen rather it is free from it. It is, in other words, a contaminant of adenovirus. AAV integrates into the genome like lentivirus yet only by doing it differently. It focuses on chromosome 19 when it is AAVS 1. This is the riskless platform for AAV vector system as it doesn’t harm the cells.
Again, both lentivirus and AAV are modified in order to make it safe and easy to use. AAV however requires co-infection with that of a helper virus and allow insertion of genes that are of length 4kb approximately although due to its smaller size it creates some challenges for some of the applications.
Lentivirus systems have been modified by scientists and microbiologists from HIV. These then undergoes transformation through generations and hence have become safe for human application. Another point about lentivirus is that the retroviral proteins make expression only during the time of packaging. This means the host cell cannot produce infectious virus thus making them quite safe. Unlike AVV virus lentivirus can deliver large DNA sequences that may be within 5 to 6 kb in length.
However, microbiologists are also making inroads wherein AAV hybrids have been developed for AAV expression system and packaging