Difference between revisions of "Team:Austin LASA/Description"

Revision as of 02:01, 18 October 2018

const r = i => h('a', {href: '#ref_' + i}, i);
h(g.Page, {title: 'Description', prev: 'https://2018.igem.org/Team:Austin_LASA/Collaborations', next: 'https://2018.igem.org/Team:Austin_LASA/Design', selector: [2, 0]},
  h(g.Section, {title: 'Why HIV Detection in Infants?'},
    h('p', null, 'HIV diagnosis of infants in the developing world continues to pose many problems. It is estimated that there are approximately 1500 new cases of HIV infection in children under the age of 15, 90% of which occur in the developing world and contracted HIV at birth [', r(1), ']. Infants often show symptoms of HIV very early on, and in some cases, HIV can rapidly evolve into AIDS [', r(2), ']. As such, it is imperative that infants with HIV are diagnosed as early as possible.'),
    h('p', null, 'The WHO has stated that earlier diagnosis of HIV in infants and children:'),
    h('ul', null,
      h('li', null, 'enables the early identification of who have HIV-infection, as a first step in securing their treatment and care'),
      h('li', null, 'enables the identification of those who are HIV-exposed but uninfected, facilitating follow-up care and prevention measures that will help to ensure that they remain uninfected'),
      h('li', null, 'assists in the effective use of essential resources by targeting ART on children who need treatment'),
      h('li', null, 'improves the psychosocial well-being of families and children, reducing potential stigma, discrimination and psychological distress for HIV-uninfected children and increasing the chances of adoption for orphans'),
      h('li', null, 'facilitates life-planning for parents and/or children who have HIV [', r(3), ']')
    ),
    h('p', null, 'Unfortunately, HIV diagnosis in infants faces more challenges than HIV diagnosis in adults. Typical serological assays result in large false positives and negatives as infants retain maternal HIV antibodies for up to 18 months, initially obtaining them through transplacental fluid in utero or through breastfeeding milk postnatally, and are therefore unreliable for use as a diagnostic method [', r(3), ']. As a result, HIV DNA/RNA PCR tests, p24 core antigen tests, and HIV cultures are the only reliable diagnostic tests for HIV in infants [', r(3), ', ', r(4), ']. PCR tests, although reliable, are frequently unavailable in resource-constrained settings where the proper lab equipment and skilled personnel are limited [', r(5), ']. HIV cultures, similarly to PCR tests, require proper lab equipment and skilled personnel in addition to taking up to two weeks to grow and obtain results [', r(3), ']. p24 core antigen tests also require proper lab equipment and skilled personnel, but are undergoing testing and clinical evaluation for their utility [', r(5), '].')
  ),
  h(g.Section, {title: 'How Does Our Project Tie In?'},
    h('p', null, 'Recent research demonstrates CRISPR-associated enzyme Cas12a’s ability to indiscriminately cleave ssDNA following recognition and cleavage of a dsDNA target strand. This property of Cas12a has been utilized for the detection of specific nucleotide sequences [', r(6), ', ', r(7), ']. In these detection assays, Cas12a is assembled with a crRNA including a spacer sequence specific to a duplexed target strand. A fluorophore-quencher pair connected by a short ssDNA sequence is present in the same reaction. Once the Cas12a-crRNA complex is binded to and cleaves a duplexed target strand, Cas12a indiscriminately cleaves any ssDNA or RNA sequence in its vicinity, including the fluorophore-quencher pair. The released fluorophore can then be detected.'),
    h('p', null, 'We aimed to use this property of Cas12a for the detection of HIV viral DNA in infected human cells. We chose specifically to focus on HIV as:'),
    h('ol', {type: 'a'},
      h('li', null, 'There is a need for the accurate detection of HIV in infants in developing countries'),
      h('li', null, 'Following diagnosis of HIV in infants, infants can be treated accordingly'),
      h('li', null, 'HIV’s genome has been very well-documented, as opposed to the genomes of other viruses such as Zika')
    )
  ),
  h(g.Section, {title: 'What Would a Point-of-Care Diagnostic System Look Like?'},
    h('p', null, 'Our project aims to design a point-of-care HIV1 diagnostic system for infants. For actual applicability in the field, our kit would consist of three components:'),
    h('ol', null,
      h('li', null, 'Isolation of viral DNA from infected cells'),
      h('li', null, 'Isothermal amplification of DNA for greater sensitivity'),
      h('li', null, 'Detection of DNA by a Cas12a assay.')
    )
  )
  h(g.Section, {title: 'References'},
    h('p', null, '[', h('a', {id: 'ref_1'}, '1'), '] W. (2011, February 03). Antiretroviral therapy of HIV infection in infants and children. Retrieved October 16, 2018, from ', h('a', {href: 'http://www.who.int/hiv/pub/paediatric/infants/en/'}, 'http://www.who.int/hiv/pub/paediatric/infants/en/')),
    h('p', null, '[', h('a', {id: 'ref_2'}, '2'), '] Krist, A. H., & Crawford-Faucher, A. (2002, May 15). Management of Newborns Exposed to Maternal HIV Infection. Retrieved October 16, 2018, from ', h('a', {href: 'https://www.aafp.org/afp/2002/0515/p2049.html'}, 'https://www.aafp.org/afp/2002/0515/p2049.html')),
    h('p', null, '[', h('a', {id: 'ref_3'}, '3'), '] Damet, G., & Vercauteren, G. (n.d.). Early detection of HIV infection in infants and children [PDF]. Geneva: WHO.'),
    h('p', null, '[', h('a', {id: 'ref_4'}, '4'), '] Diagnosis of HIV Infection in Infants and Children Pediatric ARV. (2017, November 15). Retrieved October 16, 2018, from ', h('a', {href: 'https://aidsinfo.nih.gov/guidelines/html/2/pediatric-arv/55/diagnosis-of-hiv-infection-in-infants-and-children'}, 'https://aidsinfo.nih.gov/guidelines/html/2/pediatric-arv/55/diagnosis-of-hiv-infection-in-infants-and-children')),
    h('p', null, '[', h('a', {id: 'ref_5'}, '5'), '] Shafiee, H., Wang, S., Inci, F., Toy, M., Henrich, T. J., Kuritzkes, D. R., & Demirci, U. (2015). Emerging technologies for point-of-care management of HIV infection. Annual review of medicine, 66, 387-405.'),
    h('p', null, '[', h('a', {id: 'ref_6'}, '6'), '] Gootenberg, J. S., Abudayyeh, O. O., Kellner, M. J., Joung, J., Collins, J. J., & Zhang, F. (2018). Multiplexed and portable nucleic acid detection platform with Cas13, Cas12a, and Csm6. Science, 360(6387), 439-444.'),
    h('p', null, '[', h('a', {id: 'ref_7'}, '7'), '] Chen, J. S., Ma, E., Harrington, L. B., Da Costa, M., Tian, X., Palefsky, J. M., & Doudna, J. A. (2018). CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity. Science, 360(6387), 436-439.')
  )
);

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      )
    ),
-   h(g.Section, {title: 'What Would a Point-of-Care Diagnostic System Look Like?',
+   h(g.Section, {title: 'What Would a Point-of-Care Diagnostic System Look Like?'},
      h('p', null, 'Our project aims to design a point-of-care HIV1 diagnostic system for infants. For actual applicability in the field, our kit would consist of three components:'),
      h('ol', null,