Scientists from University of Leeds, owing to the methods of molecular engineering, have discovered a new way to detect and destroy E7 oncoprotein with the use of aptamers. This protein is connected with carcinogenesis leading to i.a. the development of cervical cancer after previous infection with HPV 16.
HPV (human papillomavirus) is a DNA virus which has the closest affinity to epithelial tissue. Over 100 types of the virus were identified, 40 of which attack the area of genitalia and anus what makes it one of the most frequent infection transmitted sexually. Every year the number of infected people increases by 14 millions. What is more, the majority of men and women who are sexually active will be infected by one the HPV type.
However, in the majority of infected people the disease does not manifest itself and even if any symptoms occur, they disappear after 2 years in 90% of people. Symptoms caused by the virus are genital warts and warts in the area of larynx and feet. HPV should be also connected with the occurrence of tumours such as cervical cancer, vulvar cancer, vaginal carcinoma, penile cancer and the tumours in the area of the head and neck. According to WHO in 2008 the number of new cervical cancer cases was 529 thousands and the number of deaths was 274 thousands. 99% was caused by HPV. Oncogenic types are: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, 82 and types of low carcinogenesis level are: : 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, CP6108.
There are many methods decreasing the risk of HPV infection. Most of them consist in the reduction of sexual contact between partners. Using protection such as condoms significantly limits the possibility of infection but it does not eliminate it completely. Staying in the relationship with one partner, as well as the reduction of sexual partners number, significantly decreases the risk of infection. Although, even a person who is in relationship with one partner throughout the whole life can be infected. It shows how common is the prevalence of HPV. Efforts of medical care should be aimed mainly to prevent negative complications of the infection.
In order to limit complications of HPV infection, an immunization system was devised against the group of high risk viruses especially types 16 and 18 which are responsible for about 70-75% cervical cancer cases.
Immunization, which is used before the sexual initiation in girls between 9 and 13 years old, is used as prophylaxis. A vaccine for boys aged 11-12 , men and women from the age of 13 to even 26 is also available in some regions of the world. Such vaccination is recommended to those people who were not vaccinated previously or persons from the increased risk groups e.g. homosexuals or bisexuals.
After entering a cell, the expression of HPV genome occurs. Types 16 and 18 are characterized by the presence of the E6 and E7 oncogenes. After the synthesis process oncoprotein E6, which is responsible for degradation of suppressor protein p53, develops. In turn, E7 oncoprotein by connecting with pRb protein prevents connection with E2F factor what is a cause for the decline of the control over G1 phase conversion to S phase of cell’s life- cycle. What is more, E7 interacts with about 30 proteins i.a. with p300 and TBP (TATA-binding protein).
The scientists were able to create RNA A2 aptamer which binds to HPV16 E7. Aptamer is a sequence of nucleic acids which, by creating spatial structure, strongly and specifically connect with target molecule thus inactivating it. Regarding their function they are similar to antibodies. However, they are much smaller, not immunogenic, and methods of their synthesis guarantee high “purity” and give high possibility of modification.
After the implementation of A2 molecules to previously prepared SiHa and CaSki cell lines, the scientists obtained promising results of in vitro studies. In SiHa cell line the decrease of cell’s survival rate due to induced apoptosis was observed. Process occurred because of A2 aptamer which impeded interaction between HPV16 E7 and pRb. In turn, in CaSki line the relationship between decrease of E7 level and the increase of pRb level was proved.
The scientists continue research aimed to create smaller and, at the same time cheaper, molecules which will additionally be able to interfere with E6 oncoprotein. The use of specific aptamers seems to be very wide starting with prophylaxis, through diagnosis, to the treatment of HPV infection consequences namely, cervical cancer.
Written by: Maciej Jakuszko, Sylwia Romanowska
Source:
1.http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0064781
2.http://www.figo.org/publications/ijgo-supplement-october-2009-supplement-1
3.http://www.cdc.gov/hpv/whatishpv.html
4.http://www.cdc.gov/std/hpv/
5.http://www.hpvcentre.net/index.php
6.http://www.who.int/immunization/topics/hpv/en/
7.http://www.hpvcentre.net/link_media/statistics_map_ICO.pdf
8.http://www.ncbi.nlm.nih.gov/pubmed/19319884
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