Gene Therapy and Small Molecules Used in the Treatment of Cystic Fibrosis
Yashwant Pathak in Gene Delivery, 2022
Adenoviruses belong to the family Adenoviridae. These are nonenveloped, double-stranded DNA viruses composed of a complex icosahedral capsid (Volpers and Kochanek, 2004) and (Saban et al., 2006). Studies realized that the coxsackie and adenovirus receptor (CAR) receptors are located on the basolateral rather than the apical membrane of airway epithelial cells that led to assessment of tight junction openers, such as sodium caprate and lysophosphatidylcholines, which showed moderate success (Griesenbach, Pytel, and Alton, 2015). The knob domain of the fiber binds to the coxsackie and adenovirus receptor (CAR) on the cell surface and facilitates virus entry, (Volpers and Kochanek, 2004) although integrin receptors, such as αvβ3 and αvβ5 and the major histocompatibility complex (MHC) class I, may also play a role in virion–cell interaction. After arrival, the virus remains in an episomal state within the nucleus. In one research study, a serotype 2 adenoviral (Ad2) vector carrying the human CFTR cDNA was administrated nasally (Griesenbach, Pytel, and Alton, 2015).
Adenovirus
Avindra Nath, Joseph R. Berger in Clinical Neurovirology, 2020
Adenoviruses that cause human disease belong to the family Adenoviridae and the genus Mastadenovirus. They are classified into six subgroups or species (formerly called subgenera), A–F, on the basis of their physiochemical, biological and genetic properties (Table 10.1) [3,4]. Adenovirus subgroups B and C are usually implicated in cases of CNS disease. Subgroups are further classified into more than 50 distinct adenoviruses (Ad) serotypes or subspecies based upon antigenic determinants detected by viral neutralization assay [5,6]. Serotypes within each subgroup are closely related at the DNA level and frequently share similar biological properties. DNA analysis using restriction serotypes endonucleases allowed the identification of subspecies that appear intermediate between established serotypes, suggesting the occurrence of viral recombination in nature and resulting in the classification of adenoviruses into several new genotypes [7]. More rapid and sensitive polymerase chain reaction (PCR) assays have identified adenovirus serotypes in a variety of clinical conditions [8,9]. Although typing of adenoviruses into subgroups and serotypes is not routinely performed in most clinical laboratories, specific identification can be of clinical and epidemiological importance [10].
Cancer-Causing Viruses
Satya Prakash Gupta in Cancer-Causing Viruses and Their Inhibitors, 2014
Adenoviruses belong to the family of Adenoviridae. They are so named because they were initially isolated from human adenoids (in 1953). They are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. In humans, more than 50 different adenovirus serotypes have been described. Adenoviruses are able to replicate in the nucleus of mammalian cells using the host’s replication machinery. Once the virus has successfully gained entry into the host cell, the endosome acidifies, altering virus topology by causing capsid components to disassociate. These changes as well as the toxic nature of the pentons result in the release of the virions into the cytoplasm. They are then transported to the nuclear pore complex with the help of cellular microtubules, whereby the adenovirus particles disassemble. Viral DNA is subsequently released, which can enter the nucleus via the nuclear pore (Meier and Greber 2004). After this, the DNA associates with histone molecules. Thus, viral gene expression can occur, and new virus particles can be generated.
Nano-vaccines for gene delivery against HIV-1 infection
Published in Expert Review of Vaccines, 2023
Shuang Li, Meng-Yue Zhang, Jie Yuan, Yi-Xuan Zhang
Adenoviridae is a family of viruses with non-enveloped, icosahedral virions containing linear dsDNA genomes of 25–48 kb [59]. Several Ads are currently being developed as potential HIV-1 vaccine candidates that rely on recombinant adenoviruses (rAds) to deliver HIV-1 immunogens [60]. The Ads possess attractive properties as viral vectors for nano-vaccine development, including efficient infection of various types of cells, low pathogenicity, strong immunogenicity, excellent biosafety, transgene incorporation capacity, and ease of manufacture and administration [61]. Of the current serotypes of Ad, human serotypes 2 and 5 have been the most prevalent gene delivery vectors. The Ad vectors tend to induce strong innate immune response by intravenous administration, and 90% of vector DNA is cleared in circulation within 24 h. The innate immune response is dose-dependent and independent of the activation state of the compartments. The Ad vectors interact with fragments of the complement component C3 or activates the complement of immunized individuals via antibodies [62]. The rAds have been widely developed as vaccines delivering antigenic gene for the prophylaxis of HIV-1 [63].
Oncolytic virus therapy for malignant gliomas: entering the new era
Published in Expert Opinion on Biological Therapy, 2023
Hirotaka Fudaba, Hiroaki Wakimoto
HSV-1 is an enveloped double-stranded liner-DNA virus of the Herpesviridae family. The HSV-1 genome is approximately 152 kb in size and encodes at least 80 open reading frames. Genetic modifications of the HSV-1 genome can eliminate toxicity to normal cells and enable the arming of various exogenous genes. Adenovirus is a non-enveloped double-stranded DNA virus of the Adenoviridae family. The well-established biology of human adenovirus type 5 leads to generating oncolytic adenovirus after genetic manipulation and modification. Vaccinia virus is an enveloped double-stranded DNA virus and belongs to the poxviridae family. H-1 parvovirus (H-1PV, ParvOryx) is a small, non-enveloped, single-stranded DNA virus of the parvoviridae family whose natural host is the rat. Humans are not naturally infected and therefore lack neutralizing antibodies [7].
Vaccines against gastroenteritis, current progress and challenges
Published in Gut Microbes, 2020
Hyesuk Seo, Qiangde Duan, Weiping Zhang
Progress has been also made in vaccine development for the other enteric viruses including astroviruses (Astroviridae), adenoviruses (Adenoviridae), and sapoviruses (Caliciviridae). Other Astroviridae members such as VA-Like and MLB-like astroviruses, Picornaviridae (silivirus, cosavirus), and Parvoviridae families (bocaviruses, bufaviruses) are also isolated from patients (usually in infants and children) with gastroenteritis. Several subunit vaccines have been investigated for prevention against astrovirus infections. In particular, a trivalent subunit vaccine for hepatitis E virus, norovirus, and astrovirus was generated by fusing together the dimeric P domains of the three viruses to form a tetramer.93 When intranasally administered to mice, this trivalent product induced significant neutralizing antibody responses to the P domains of all three viruses. Another subunit astrovirus vaccine candidate used the capsid protein (CP) of mink astrovirus elicited high levels of serum anti-CP antib odies and lymphoproliferation responses and also stimulated IFN-γ levels in mice.94 Importantly, it was observed that virus shedding was suppressed and clinical signs including severe diarrhea were reduced in the litters born to the immunized mink mothers when challenged with a heterogeneous astrovirus strain.94 Future human volunteer studies and clinical trials are needed to assess the efficacy of these vaccine candidates against viral gastroenteritis.
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