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Dnai for the modulation of genes 
Aberrant gene expression, for example overexpression or expression of mutant genes and proteins, is the root cause of many diseases. Cancer is a result of aberrant cellular signaling that causes uncontrolled growth and proliferation; as a complex disease, combination proteins involving angiogenesis, epithelial to mesenchymal transition, tumor suppression, cell cycle, metastasis, invasion, differentiation, apoptosis, autophagy, adhesion, hypoxia, inflammation, immune response, necrosis, growth, proliferation, tolerance and more may be affected in cancer. Other non-cancerous diseases that involve abnormal protein products include cardiovascular, metabolic, inflammatory, genetic, bowel, fungal, dermatological, dental, oral, vascular, endocrine, nephrologic, orthopedic, podiatric, pulmonary, and musculoskeletal diseases, among others. Many therapeutic agents take advantage of this concept and are designed to target and inhibit dysregulated proteins. Another therapeutic concept involves directly targeting and modulating gene expression using non-coding nucleic acids. Previous issues of antisense therapies include large dose requirements, non-specific effects, phosphothioates oligonucleotide sulfur toxicity, delivery and the high cost associated with these obstacles. In a 2013 patent application, ProNAi Therapeutics Inc presented oligonucleotide technology for optimized modulation of gene expression that resolves a number of these problems.
The presented oligonucleotides vary in composition and target binding sites. Composition variants include CG content, secondary structures, length, target region homology, CpG island targeting, cytosine modification, base modification for degradation prevention and more. Different oligonucleotides were designed to bind to transcription factor binding sites or regulatory elements; some oligonucleotides were designed to interfere with gene trasnciption and others with gene expression. Examples of genes to which the invention hybridized include Survivin, STAT3, HIF1A, KRAS, ApoB, MEK1-2, CD4, WNT1, PD-1, TNF-a, HBV, PARP1, ERBB2, CD68, FGFR1, JAK2 and more. Effects of oligonucleotides included modulation in proliferation, cell phenotype, related-gene expression, cell signaling, related-gene transcription. Gene expression products encompasses both protein products and nucleic acid products such as rRNA, tRNA, snRNA or other RNA. The oligonucleotides were examined across species cells, cancer cell types and non-cancer cell types. Optimal delivery methods for the oligonucleotides were also presented and include liposome encapsulation, a ligand/cell targeting compound, nanoparticles and nanocrystals; delivery methods were further modified based on situational needs.
As with any thorough, in-depth project, patent applications require a substantial amount of work and verification. Altogen Labs was involved in this process, performing services including: HepG2, A549, MDA-MB-231, and DU145 cell culture work. Types of experiments performed include qRT-PCR, viability assays, RNA isolation, phenotype monitoring, oligonucleotide treatment, mRNA expression analysis, and cell growth inhibition assays. Altogen Labs is an Austin, Texas based preclinical contract research company dedicated to providing top-notch services for a wide customer base including academic publications, patent applications, IND applications, regulatory submissions, drug development and more. A trained team of expert scientists at Altogen Labs is available for every step of the research process including instant quotes, experimental development, biology and preclinical research studies and results analysis. Apart from the assays outlined in this patent application, Altogen Labs also offers other in vitro and in vivo services with over 100 cell models. Toxicology safety studies, liposome encapsulation, cryopreservation, cell banking, xenograft studies, and development of stable cell lines (for gene function and gene expression analysis) are some of the most popular services. Altogen Labs is compliant with Good Laboratory Practice (GLP) and happy to discuss and accomodate individual client needs (contact us at info@altogenlabs.com).