I wanted to know how ONYX-015 cells work, and their actual role in killing of cancerous cells.
Hello Rishab,
ONYX-015, or dl1520, is an adenovirus mutant that lacks the E1B 55K gene, and therefore cannot neutralize p53 during infection . In tumor cells that lack functional p53, E1B 55K should be dispensable, and, according to this hypothesis, ONYX-015 should replicate efficiently in cancer cells and kill them. Furthermore, the virus should spread to neighboring tumor cells and continue spreading until it reaches normal cells.
For adenovirus replication to occur, the host cell must be induced into S-phase by viral proteins interfering with cell cycle proteins. The adenoviral E1A gene is responsible for inactivation of several proteins, including retinoblastoma, allowing entry into S-phase. The adenovirus E1B55kDa gene cooperates with another adenoviral product, E4ORF6, to inactivate p53, thus preventing apoptosis. It was initially proposed that an adenovirus mutant lacking the E1B55kDa gene, dl1520 (ONYX-015), could replicate selectively in p53 deficient cells.
A conditionally replicative adenovirus (CRAd) with a 24 base pair deletion in the retinoblastoma-binding domain of the E1A protein (Ad5- Δ24E3), is unable to silence retinoblastoma, and therefore unable to induce S-phase in host cells.[5] This restricts Ad5-Δ24E3 to replication only in proliferating cells, such as tumour cells.
See ref. for details dear..
http://www.nature.com/onc/journal/v19/n56/full/1204096a.html
Hope it helps..!
Sir, but researches have shown that E4orf6 is by itself able to block the action of p53. Could you please explain this?
http://jvi.asm.org/content/72/12/9479.long
Dear Rishabh,
In research you will get many articles in favor as well as contradicting a perticular hypothesis so you may encounter two different articles with conflicting views on any topic. In that case do rely on the impact of the journals always. Here in the above mentioned Nature article they people have mentioned that E1B55kDa and E4ORF6 cooperate to inactivate p53. The article you have mentioned is published in December 1998 while the article I have cited is for year 2000. So a 2 year advancement is there. So in 1998 the notion might be that E4orf6 is able to block the action of p53 by itslef only but in 2000 it is a direct speculation by this Nature article that E1B55kDa gene cooperates with E4orf6 to ultimately prevent apoptosis. So in a nutshell you can say that before 2000 it was thought that E4orf6 functions independently but in 2000 it was proved that it works in collaboration with E1B55kDa. Hope it's clear to you now dear Rishabh..!
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