Frontiers in Clinical Drug Research-Anti Infectives

Volume: 1

Antisense Oligonucleotides-Based Therapeutics for Pathogenic Bacteria and Viruses

Author(s): Hui Bai, Yu You, Xiaochen Bo, Shengqi Wang and Xiaoxing Luo

Pp: 53-157 (105)

DOI: 10.2174/9781608058549114010005

* (Excluding Mailing and Handling)

Abstract

Human pathogenic bacteria and viruses are significant etiology of different types of infectious diseases that cause extremely high morbidity and mortality worldwide. Continuous failure of anti- pathogen/infective agents and therapies, as well as the paucity of postexposure therapeutics greatly facilitates the emergence and dissemination of pathogenic bacterial isolates and virus phenotypes with multi-drug resistance (MDR) or pan-drug resistance (PDR). Additionally, the potential use of these bacteria and viruses in acts of bioterrorism poses tremendous threat to global security. Novel counterstrike strategy of using single-stranded antisense oligonucleotides (ASOs) as prospective gene silencers has been a major area of anti-infective study, leading a potential revolution in the development of antibacterial and antiviral therapeutics by addressing the targets that are “undruggable” for traditional pharmaceutical approaches. Given 30 years of technology advances in elucidation of antisense mechanism, characterization of ASOs chemical modification, and refinement of delivery systems, ASOs based anti-infective strategy displays advantageous features of conceptual simplicity, straightforward designing and quick drug identification methods. The stericblocking ASOs offer improving sequence-specific anti-infective effects in vitro and in animal models of fatal infections, which enables themselves candidates for pre-clinical and clinical tests. This chapter puts together and discusses the important advances in the field based on the above mentioned technologies and the latest development of potential targets and therapeutic AS-ODNs that have reached clinical trials with antibacterial or antiviral protocols.


Keywords: Acyl carrier protein, antisense antibacterial, antisense antiviral, antisense oligonucleotides therapy, cell penetrating peptide, host factors, liposome, locked nucleic acid, peptide nucleic acid, phosphorodiamidate morpholino oligomers, phosphorothioate, RNA polymerase σ70, RNase H activation, steric-blokcing mechanism.

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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309779056 and j.to_ip >=309779056 )) and ((j.from_date <= 1739848046 and j.to_date >= 1739848046 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 6434) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309779056 and j.to_ip >=309779056 )) and ((j.from_date <= 1739848046 and j.to_date >= 1739848046 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 6434) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309779056 and j.to_ip >=309779056 )) and ((j.from_date <= 1739848046 and j.to_date >= 1739848046 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 6434)
      920μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 1507 and `b`.`banner_from_date` <= 1739848046 and `b`.`banner_to_date` >= 1739848046 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.49msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 1507
      • 3: 1739848046
      • 4: 1739848046
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='049c394f3d966f3fd886b505f3a4ae28'
      270μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    14Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        4oEoz743SpNPro1M835AZ9vvJ4EO5kHBQtHYuvNq
        uc_cart_id
        049c394f3d966f3fd886b505f3a4ae28
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/6434" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/6434
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:16 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        []
        
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 18 Feb 2025 03:07:26 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IktzZElzckZrZTlhVGh5V0I5VTJubWc9PSIsInZhbHVlIjoiYlBHZkp6bEswbkdtVy9XWnUwQ2plTU4vb28rYnRyTmYyWnpEcHZIMUorcDBoT0YvWlZaWkZjZENuRklLNHZJczVJbHQ0M0ZvcTgvUDNqOFVGNmd0NzhoUXNxdVR0YThmN2Q0bDAwQjNWbzd3YXg3WURXRjVPdTVud2N5TC9VbTMiLCJtYWMiOiI0NDRhNTEwZTJiOTIyYzY2OTQ1YWMzMmFjZjgyM2Y3ZDc0MDc1ZDFlOWI4YTc4MzM2MzUyODQ5ODU1OTNmMDI4IiwidGFnIjoiIn0%3D; expires=Thu, 20 Feb 2025 15:07:26 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IktzZElzckZrZTlhVGh5V0I5VTJubWc9PSIsInZhbHVlIjoiYlBHZkp6bEswbkdtVy9XWnUwQ2plTU4vb28rYnRyTmYyWnpEcHZIMUorcDBoT0YvWlZaWkZjZENuRklLNHZJczVJbHQ0M" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImFVUWF6WWhTMmVVOFB6cks3dmxOdmc9PSIsInZhbHVlIjoiRzJQUTVqSGNWaDNEL05ZdW9SN2o3dTJwV0pyY1FPbXY1NUF6ZEd1TDU1RzlmdlM3RlhRbHkrd2lCR3BIcE5aV2VMWjlRbW1qVUJ5akZuV2JVNDV3ZjZsbW13NDlXRzMwQWVoWVlTcFlmUnB0MXlOdHRQZThIZDJ1clMvWlM5SWoiLCJtYWMiOiI5MTdjNGIwNjIzYmQ0YTc3NTEwOWMxMDA5YmJhNDVmMzg0NmYyN2FhZTFmZWE4ZDA4OTJkOWVjYTE4OWQ4ZmU4IiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6ImFVUWF6WWhTMmVVOFB6cks3dmxOdmc9PSIsInZhbHVlIjoiRzJQUTVqSGNWaDNEL05ZdW9SN2o3dTJwV0pyY1FPbXY1NUF6ZEd1TDU1RzlmdlM3RlhRbHkrd2l" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IktzZElzckZrZTlhVGh5V0I5VTJubWc9PSIsInZhbHVlIjoiYlBHZkp6bEswbkdtVy9XWnUwQ2plTU4vb28rYnRyTmYyWnpEcHZIMUorcDBoT0YvWlZaWkZjZENuRklLNHZJczVJbHQ0M0ZvcTgvUDNqOFVGNmd0NzhoUXNxdVR0YThmN2Q0bDAwQjNWbzd3YXg3WURXRjVPdTVud2N5TC9VbTMiLCJtYWMiOiI0NDRhNTEwZTJiOTIyYzY2OTQ1YWMzMmFjZjgyM2Y3ZDc0MDc1ZDFlOWI4YTc4MzM2MzUyODQ5ODU1OTNmMDI4IiwidGFnIjoiIn0%3D; expires=Thu, 20-Feb-2025 15:07:26 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IktzZElzckZrZTlhVGh5V0I5VTJubWc9PSIsInZhbHVlIjoiYlBHZkp6bEswbkdtVy9XWnUwQ2plTU4vb28rYnRyTmYyWnpEcHZIMUorcDBoT0YvWlZaWkZjZENuRklLNHZJczVJbHQ0M" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImFVUWF6WWhTMmVVOFB6cks3dmxOdmc9PSIsInZhbHVlIjoiRzJQUTVqSGNWaDNEL05ZdW9SN2o3dTJwV0pyY1FPbXY1NUF6ZEd1TDU1RzlmdlM3RlhRbHkrd2lCR3BIcE5aV2VMWjlRbW1qVUJ5akZuV2JVNDV3ZjZsbW13NDlXRzMwQWVoWVlTcFlmUnB0MXlOdHRQZThIZDJ1clMvWlM5SWoiLCJtYWMiOiI5MTdjNGIwNjIzYmQ0YTc3NTEwOWMxMDA5YmJhNDVmMzg0NmYyN2FhZTFmZWE4ZDA4OTJkOWVjYTE4OWQ4ZmU4IiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6ImFVUWF6WWhTMmVVOFB6cks3dmxOdmc9PSIsInZhbHVlIjoiRzJQUTVqSGNWaDNEL05ZdW9SN2o3dTJwV0pyY1FPbXY1NUF6ZEd1TDU1RzlmdlM3RlhRbHkrd2l" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "4oEoz743SpNPro1M835AZ9vvJ4EO5kHBQtHYuvNq" "uc_cart_id" => "049c394f3d966f3fd886b505f3a4ae28" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/6434" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-18 03:07:26GET/chapter/64341121916