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Dr. Wayengera, Misaki MBChB, MSc Bio-Entrepr.Equiv., PhD Candidate
Asst. Lecturer, Genetics & Genomics, Depts of Pathology & Medical Microbiology

Research interests: R-M enzymatic therapeutics and Pathogen- Omics

  1. R-M enzymatic therapeutics

 

  1. A historical re-cap: Although the restriction enzyme (REase) components of bacteria R-M systems-machinery have gained widespread use in molecular cloning and or biology as natural scissors for inserting targeted incisions and excisions in DNA, the primary evolutionary role of R-M systems is that of an immunological defense of bacteria genomes against infectious tropism by phages. In 1999, appreciating the abundance, and role of the restriction modification (R-M) systems-machinery in bacteria, as a primitive-defense against parasitism of bacteria cellular genomes by a type of bacteria infecting viruses called: bacteriophages; I first proposed its use as a model for research and development of novel anti-viral peptides against human viruses of either native (eg. Herpes Simplex Viruses-HSVs types 1 & 2; and Human papillomaviruses -HPVs types, -16 & -18) or transient (e.g proviral HIV) dsDNA nature. In 2003, we published our first, really less renowned paper on this subject [Wayengera, M. Makerere Med J. 38, 28-30 (2003)]. This was followed, in 2005, by an oral presentation at the Regional students Conference on ARVs& latest development in HIV care (RCAH) held in Kampala, Uganda on Feb 9-12th [Wayengera M. RCAH abstract book pg 18-19].  The former was quickly followed by press coverage in the local daily New Vision [Makerere develops model for AIDS cure. Tuesday 1st March]. By 2006, it was clear that more acumen and alchemy were required to push this through than were then present on ground. It then that I moved to Toronto Canada, where at the MaRS discovery district-UHN, U of T; through the Bio-entrepreneurship program, and guidance of Nina Chagnon and Gary L. Madsen (Promega Corporation, Phil-USA)-we conducted our first study to report frequency and  site mapping of HIV/SIV gene cleavage by various bactera restriction endonucleases (REases)[ Wayengera, M., Kajumbula, H., & Byarugaba, W. Afr J Biotechnol. 6(10), 1225-1232 (2007)]. This was followed by two models for ex-vivo application as microbicides: (i) nano-conjugates [Wayengera, M. Afr J Biotechnol.  6(10), 1221-1224 (2007)] and or, live-microbicides [Wayengera, M. Afr J Biotechnol. 6(15), 1750-1756 (2007)]. This cemented the era of R-M enzymatic therapeutics [Wayengera, M. Afr J Biotechnol.7 (12), 1791–1796 (2008)] and led to the description of pre-integration viral genome slicing (or simply PRINT-GSX) as an alternate or complimentary gene therapy module to RNA interference [Wayengera, M. J Appl. Biol. Sci. 1(2), 56-63 (2008)]. Around this time, we also identified enzymes cleaving HSV-2 [Wayengera, M., Kajumbula, H., Byarugaba, W. BMC Theor Biol Med Model. 5,18 (2008)]. That said, we still had major limitations.
  1. A fast-forward into the future: The Science-historian-Thomas Kuhn has observed that: “science advances only when there is a paradigm- shift; that is, the older theoretical frame-work is proven limited, and new theories are sought”.  And our paradigm-shift was: because of the small size of the phage-genomes, bacteria-in order to enhance the efficiency of their (R-M) natural anti-phage defense, have only evolved REases with smaller palindrome recognizing ability.  Therefore, most of our above identified highly slicing (SX) REases against human viruses (HIV-dsDNA, HSV-2) equally targeted palindromic sequences naturally found within the human genome. The issuing off target host-genome-toxicity; was a particularly major limitation to the in-vivo application of R-M therapeutics. A long-term goal in the field of R-M enzymatic therapeutics has, thus been to generate synthetic restriction- endonucleases with longer recognition sites specific to only the eukaryotic virus, by mutating or engineering existing enzymes.

 

To this end, we are working with zinc finger nucleases as anti-viral therapeutics. [Wayengera, M. Identity of Zinc Finger Nucleases with Specificity to Herpes Simplex Virus type II Genomic DNA: Novel HSV-2 Vaccine/ Therapy Precursors. BMC Theor Biol Med Model. 8, 20 (2011)].

 

  1. Pathogen- Omics

According to the all-time-constant mathematician Richard Hamming, it is unwise for any aspiring great scientist to focus on one problem. Following this advise - I am also working on:

  1. TB Biomarkers [Wayengera, M. BMC Theor Biol Med Model., 6,  4 (2009)].
  2. Malaria Gene-therapeutic Vaccines; Smart-insecticides and Mosquito Biomarkers: [Byarugaba W, Kajumbula H, Wayengera M. BMC Theor Biol Med Model 6, 14 (2009)]
  3. Ebola, Influenza & HIV Transmission Dynamics [Wayengera, M. et al . J  Appl Biol Sci 10, 471 - 482 (2008); Wayengera, M., et al . Afr, J. Biotech 8(10), 2125-2130 (2009); Wayengera, M. et al. Afr, J. Biotech 8(17), 4025-4031(2009); Wayengera, M. Theor Biol Med Model 2010, 7: 5].
  4. Neglected tropical diseases e.g EMF [Wayengera, M. PLoS ONE 2009; 4(10): e7420]
  5. Reviews: [Wayengera M Bone Marrow Transplantation(BMT) and Gene replacement Therapy(GRT) in Sickle Cell Anemia Niger J of Med 2008; 17(3):251-256; Wayengera M. Targeting persistent HIV: Where and how, if possible? Elsevier HIV & AIDS Review 2011,10: 1-8 Wayengera M, Kajumbula H. ,Byarugaba W. Harnessing pharmacogenomics to tackle resistance to the “Nucleoside Reverse Transcriptase Inhibitor” backbone of highly active antiretroviral therapy in resource limited settings Open AIDS Journal 2008, 2:78-81 ]
 
     
 
 
 

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