Viral gene therapy

Abstract

Cancer is a multigenic disorder involving mutations of both tumor suppressor genes and oncogenes. A large body of preclinical data, however, has suggested that cancer growth can be arrested or reversed by treatment with gene transfer vectors that carry a single growth inhibitory or pro-apoptotic gene or a gene that can recruit immune responses against the tumor. Many of these gene transfer vectors are modified viruses. The ability for the delivery of therapeutic genes, made them desirable for engineering virus vector systems. The viral vectors recently in laboratory and clinical use are based on RNA and DNA viruses processing very different genomic structures and host ranges. Particular viruses have been selected as gene delivery vehicles because of their capacities to carry foreign genes and their ability to efficiently deliver these genes associated with efficient gene expression. These are the major reasons why viral vectors derived from retroviruses, adenovirus, adeno-associated virus, herpesvirus and poxvirus are employed in more than 70% of clinical gene therapy trials worldwide. Because these vector systems have unique advantages and limitations, each has applications for which it is best suited. Retroviral vectors can permanently integrate into the genome of the infected cell, but require mitotic cell division for transduction. Adenoviral vectors can efficiently deliver genes to a wide variety of dividing and nondividing cell types, but immune elimination of infected cells often limits gene expression in vivo. Herpes simplex virus can deliver large amounts of exogenous DNA; however, cytotoxicity and maintenance of transgene expression remain as obstacles. AAV also infects many non-dividing and dividing cell types, but has a limited DNA capacity. This review discusses current and emerging virusbased genetic engineering strategies for the delivery of therapeutic molecules or several approaches for cancer treatment.

Intranasal Vaccination of Recombinant Adeno-Associated Virus Encoding Receptor-Binding Domain of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Spike Protein Induces Strong Mucosal Immune Responses and Provides Long-Term Protection against SARS-CoV Infection

“…and i.n. routes, following the protocols described previously with some modifications (42)(43)(44). For the i.m.…”

Analysis of poration-induced changes in cells from laser-activated plasmonic substrates

“…Among biological methods, viral transduction offers high efficiency but has limited cargo-carrying capacity and immunotoxicity risks [1][2][3]. Chemical methods such as lipofection have high throughput but vary in efficiency [4].…”

Kök hücrede gen transferi ile istenen bir genin aktivasyonu veya susturulması uygulamalarının rejeneratif tıpta kullanımı

“…Viral vektörler özellikle hızla bölünen hücreleri tercih ettiğinden dolayı kanser hücreleri ile olan gen tedavi uygulamalarında kullanım alanı bulmuştur. "nucleofection" yöntemi ise özellikle bölünmeyen (örneğin nöral hücreler) gen aktarımında önemli avantajlar sağlamaktadır [12,13].…”