{"id":6675,"date":"2025-09-11T15:14:14","date_gmt":"2025-09-11T05:44:14","guid":{"rendered":"https:\/\/hepatitissa.asn.au\/communitynews\/?p=6675"},"modified":"2025-09-17T10:41:29","modified_gmt":"2025-09-17T01:11:29","slug":"cutting-out-hep-b-with-molecular-scissors","status":"publish","type":"post","link":"https:\/\/hepatitissa.asn.au\/communitynews\/2025\/09\/cutting-out-hep-b-with-molecular-scissors\/","title":{"rendered":"Cutting Out Hep B with &#8216;Molecular Scissors&#8217;"},"content":{"rendered":"\n<p class=\"has-drop-cap\">A genetic peculiarity that is sometimes found in biochemistry is &#8216;<a href=\"https:\/\/en.wikipedia.org\/wiki\/CccDNA\" target=\"_blank\" rel=\"noreferrer noopener\">covalently closed circular DNA<\/a>&#8216; (cccDNA), where the DNA molecule, instead of being a long, ribbon-like strand, becomes a closed loop. Since many medical treatments involve attacking unwanted DNA at its vulnerable open end-points, cccDNA, which has no such open end-points, is much harder to target.<\/p>\n\n\n\n<p>Unfortunately, the hepatitis B virus (HBV) exists as rings of cccDNA in the human body, which is one reason it has been so hard develop an effective cure for the disease. Medications can suppress HBV activity but cannot eliminate this stubborn form of viral DNA, which hides inside infected liver cells and fuels relapse when treatment stops.<\/p>\n\n\n\n<figure data-wp-context=\"{&quot;imageId&quot;:&quot;69d73bb0312ae&quot;}\" data-wp-interactive=\"core\/image\" data-wp-key=\"69d73bb0312ae\" class=\"wp-block-image aligncenter size-full is-resized wp-lightbox-container\"><img loading=\"lazy\" decoding=\"async\" width=\"326\" height=\"154\" data-wp-class--hide=\"state.isContentHidden\" data-wp-class--show=\"state.isContentVisible\" data-wp-init=\"callbacks.setButtonStyles\" data-wp-on--click=\"actions.showLightbox\" data-wp-on--load=\"callbacks.setButtonStyles\" data-wp-on-window--resize=\"callbacks.setButtonStyles\" src=\"https:\/\/hepatitissa.asn.au\/communitynews\/wp-content\/uploads\/2025\/09\/HAT1-signaling-confers-to-the-regulation-of-HBV-cccDNA-minichromosome-In-this-model.png\" alt=\"\" class=\"wp-image-6677\" style=\"width:443px;height:auto\" srcset=\"https:\/\/hepatitissa.asn.au\/communitynews\/wp-content\/uploads\/2025\/09\/HAT1-signaling-confers-to-the-regulation-of-HBV-cccDNA-minichromosome-In-this-model.png 326w, https:\/\/hepatitissa.asn.au\/communitynews\/wp-content\/uploads\/2025\/09\/HAT1-signaling-confers-to-the-regulation-of-HBV-cccDNA-minichromosome-In-this-model-300x142.png 300w\" sizes=\"auto, (max-width: 326px) 100vw, 326px\" \/><button\n\t\t\tclass=\"lightbox-trigger\"\n\t\t\ttype=\"button\"\n\t\t\taria-haspopup=\"dialog\"\n\t\t\taria-label=\"Enlarge\"\n\t\t\tdata-wp-init=\"callbacks.initTriggerButton\"\n\t\t\tdata-wp-on--click=\"actions.showLightbox\"\n\t\t\tdata-wp-style--right=\"state.imageButtonRight\"\n\t\t\tdata-wp-style--top=\"state.imageButtonTop\"\n\t\t>\n\t\t\t<svg xmlns=\"http:\/\/www.w3.org\/2000\/svg\" width=\"12\" height=\"12\" fill=\"none\" viewBox=\"0 0 12 12\">\n\t\t\t\t<path fill=\"#fff\" d=\"M2 0a2 2 0 0 0-2 2v2h1.5V2a.5.5 0 0 1 .5-.5h2V0H2Zm2 10.5H2a.5.5 0 0 1-.5-.5V8H0v2a2 2 0 0 0 2 2h2v-1.5ZM8 12v-1.5h2a.5.5 0 0 0 .5-.5V8H12v2a2 2 0 0 1-2 2H8Zm2-12a2 2 0 0 1 2 2v2h-1.5V2a.5.5 0 0 0-.5-.5H8V0h2Z\" \/>\n\t\t\t<\/svg>\n\t\t<\/button><figcaption class=\"wp-element-caption\">Simplified image of the hepatitis B cccDNA rings [<a href=\"https:\/\/www.researchgate.net\/figure\/HAT1-signaling-confers-to-the-regulation-of-HBV-cccDNA-minichromosome-In-this-model_fig6_336246267\" target=\"_blank\" rel=\"noreferrer noopener\">Image used via CC license<\/a>]<\/figcaption><\/figure>\n\n\n\n<p>Now a new research project in South Africa, at the <a href=\"https:\/\/www.wits.ac.za\/\" target=\"_blank\" rel=\"noreferrer noopener\">University of the Witwatersrand<\/a>, Johannesburg, has made use of a new technology to try to overcome this problem. In South Africa, there are an estimated 2.5 million people living with hepatitis B, out of 54 million: this is almost 5% of the population.<\/p>\n\n\n\n<p>This research, which is yet to be tested on humans, is showing that the genetic blueprint of the hepatitis B virus (HBV) could be permanently inactivated with newly engineered molecular &#8220;scissors&#8221; called TALENs. These &#8216;<a href=\"https:\/\/en.wikipedia.org\/wiki\/Transcription_activator-like_effector_nuclease\" target=\"_blank\" rel=\"noreferrer noopener\">transcription activator-like effector nucleases<\/a>&#8216; are enzymes that can be engineered to cut very specific sequences of DNA, which can be used to attack the ring structure of the cccDNA.<\/p>\n\n\n\n<figure data-wp-context=\"{&quot;imageId&quot;:&quot;69d73bb031ad6&quot;}\" data-wp-interactive=\"core\/image\" data-wp-key=\"69d73bb031ad6\" class=\"wp-block-image aligncenter size-full is-resized wp-lightbox-container\"><img loading=\"lazy\" decoding=\"async\" width=\"459\" height=\"432\" data-wp-class--hide=\"state.isContentHidden\" data-wp-class--show=\"state.isContentVisible\" data-wp-init=\"callbacks.setButtonStyles\" data-wp-on--click=\"actions.showLightbox\" data-wp-on--load=\"callbacks.setButtonStyles\" data-wp-on-window--resize=\"callbacks.setButtonStyles\" src=\"https:\/\/hepatitissa.asn.au\/communitynews\/wp-content\/uploads\/2025\/09\/Genetic_engineering_logo.png\" alt=\"\" class=\"wp-image-6676\" style=\"width:367px;height:auto\" srcset=\"https:\/\/hepatitissa.asn.au\/communitynews\/wp-content\/uploads\/2025\/09\/Genetic_engineering_logo.png 459w, https:\/\/hepatitissa.asn.au\/communitynews\/wp-content\/uploads\/2025\/09\/Genetic_engineering_logo-300x282.png 300w\" sizes=\"auto, (max-width: 459px) 100vw, 459px\" \/><button\n\t\t\tclass=\"lightbox-trigger\"\n\t\t\ttype=\"button\"\n\t\t\taria-haspopup=\"dialog\"\n\t\t\taria-label=\"Enlarge\"\n\t\t\tdata-wp-init=\"callbacks.initTriggerButton\"\n\t\t\tdata-wp-on--click=\"actions.showLightbox\"\n\t\t\tdata-wp-style--right=\"state.imageButtonRight\"\n\t\t\tdata-wp-style--top=\"state.imageButtonTop\"\n\t\t>\n\t\t\t<svg xmlns=\"http:\/\/www.w3.org\/2000\/svg\" width=\"12\" height=\"12\" fill=\"none\" viewBox=\"0 0 12 12\">\n\t\t\t\t<path fill=\"#fff\" d=\"M2 0a2 2 0 0 0-2 2v2h1.5V2a.5.5 0 0 1 .5-.5h2V0H2Zm2 10.5H2a.5.5 0 0 1-.5-.5V8H0v2a2 2 0 0 0 2 2h2v-1.5ZM8 12v-1.5h2a.5.5 0 0 0 .5-.5V8H12v2a2 2 0 0 1-2 2H8Zm2-12a2 2 0 0 1 2 2v2h-1.5V2a.5.5 0 0 0-.5-.5H8V0h2Z\" \/>\n\t\t\t<\/svg>\n\t\t<\/button><figcaption class=\"wp-element-caption\">A simplified image of a section of DNA being cut out by a TALEN [<a href=\"https:\/\/en.wikipedia.org\/wiki\/File:Genetic_engineering_logo.png\" target=\"_blank\" rel=\"noreferrer noopener\">Image by Aircorn, used uder CC license<\/a>]<\/figcaption><\/figure>\n\n\n\n<p>Dr\u00a0<a href=\"https:\/\/www.wits.ac.za\/agtru\/team-members\/\" target=\"_blank\" rel=\"noreferrer noopener\">Tiffany Smith<\/a>, a postdoctoral research fellow at the university&#8217;s Antiviral Gene Therapy Research Unit, developed this idea. She used the TALENs because, unlike some other genetic editing techniques, they are highly effective even in complex or tightly packed DNA regions, like cccDNA rings. Smith and her team specialise in delivering mRNA in <a href=\"https:\/\/en.wikipedia.org\/wiki\/Lipid-based_nanoparticle\" target=\"_blank\" rel=\"noreferrer noopener\">lipid nanoparticles<\/a>, a platform that has already dramatically advanced vaccine development. By combining this delivery system with the precision of TALEN-based molecular scissors, they have taken an important step towards a functional cure for HBV.<\/p>\n\n\n\n<p>\u201cThe ability to target the virus\u2019s genetic blueprint directly paves the way for reduced healthcare costs and dramatically improved outcomes,\u201d Dr Smith explained.<\/p>\n\n\n\n<p>Laboratory tests on cultured human liver cells showed that the treatment reduced hepatitis B markers by 80%. In HBV-infected mice, a single dose resulted in a massive 99% reduction in circulating viral DNA. Importantly, the therapy was well tolerated, causing only mild inflammation that quickly resolved with no significant toxicity.<\/p>\n\n\n\n<p>\u201cThese results are highly promising,\u201d said Professor\u00a0<a href=\"https:\/\/www.wits.ac.za\/agtru\/team-members\/\" target=\"_blank\" rel=\"noreferrer noopener\">Patrick Arbuthnot<\/a>, who leads the Antiviral Gene Therapy Research Unit team. \u201cThis work underscores the enormous potential of gene-editing technologies to confront persistent viral infections with precision and safety.\u201d<\/p>\n\n\n\n<p>The researchers now need to demonstrate that these TALENs can accurately target viral DNA while causing few or no changes to the host\u2019s DNA. However, the ability to directly cut and disable HBV\u2019s hidden genetic blueprint, especially its stubborn cccDNA, represents a milestone in the global effort to eliminate hepatitis B.<\/p>\n\n\n\n<p>The\u00a0<a href=\"https:\/\/www.mdpi.com\/1999-4915\/17\/8\/1090\" target=\"_blank\" rel=\"noreferrer noopener\">study<\/a>\u00a0is published in the journal\u00a0<em>Viruses<\/em>.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<p><em>You may also be interested in this piece on how Hepatitis B DNA splicing may serve as an <a href=\"https:\/\/hepatitissa.asn.au\/communitynews\/2018\/10\/new-liver-cancer-markers-promises-earlier-diagnosis-and-better-outcomes\/\">early marker for liver cancer.<\/a><\/em><\/p>\n\n\n\n<p><\/p>\n","protected":false},"excerpt":{"rendered":"<p>A genetic peculiarity that is sometimes found in biochemistry is &#8216;covalently closed circular DNA&#8216; (cccDNA), where the DNA molecule, instead of being a long, ribbon-like strand, becomes a closed loop. &hellip;<\/p>\n","protected":false},"author":3,"featured_media":6678,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_FSMCFIC_featured_image_caption":"","_FSMCFIC_featured_image_nocaption":"","_FSMCFIC_featured_image_hide":"","footnotes":""},"categories":[11],"tags":[39,34],"issue":[],"ppma_author":[57],"class_list":["post-6675","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-policies-research","tag-treatment","tag-hepatitis-b"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.2 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Cutting Out Hep B with &#039;Molecular Scissors&#039; | HepSA Community News<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" 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