Biotech World

Protein engineering for Disease Control

Protein engineering is the method of production and design of new protein from natural protein/amino acid sequence using recombinant DNA technology. Nowadays protein engineering has huge impact on biotechnology and biopharmaceuticals as it has a potential to control and treat chronic diseases as protein is the workhorse of human body. Protein engineering includes various methods such as site directed mutagenesis, x-ray crystallography, DNA shuffling, random mutagenesis, homology modeling, cell surface and phage display technology, flow cytometry, molecular dynamics, computational protein design etc. Using these methods protein engineering alters protein structure to achieve functional changes such as decreased product inhibition, better substrate sensitivity, higher catalytic rates, desired cofactor use and reduced substrate competition [1]. The proteins engineered by this method can be used as therapeutic proteins to treat and control diseases which makes these very important in pharmaceutical and biotech industry.

Cancer treatment: Conventional protein engineering along with recombinant DNA technology offers intriguing possibilities for development of multifunctional and smart drug vehicles at nanoscale for the treatment of cancer and other genetic diseases. Currently cancer research involves development of specific agents for targeted delivery of imaging probes and drugs to different tumor sites. Phage display is a powerful protein engineering technology that involves selection and cloning of peptides that are displayed on the surface of bacteriophage [2]. This phage display technology isolates tumor homing peptides by in vivo phage display library screening against tumor vasculature that have huge potential as targeting probes for tumor molecular imaging and drug delivery. Protein engineering involves production of recombinant immunotoxins by fusion of variable regions of “cancer specific antibodies” with the truncated bacterial or plant toxins [3]. These immunotoxins have been shown to cause the regression of human tumor xenografts grown in mouse model. Protein engineering also utilizes complement invasion to increase complement fixing or to enhance complement dependent cell cytotoxicity (CDC) or to reverse complement resistance for cancer therapy, because cancer cells show overexpression of complement inhibitory proteins such as CD46, CD55, and CD59 in breast, lungs and other types of cancer [4].

Cardiovascular Therapeutics: Protein engineering also has a huge impact on cardiovascular therapeutics/cardiac regeneration and disease treatment advancement to specifically enhance the efficacy of molecules for cardiac repair. Recently a number of engineered proteins have been used to treat cardiovascular diseases in clinical trials such as tumor necrosis factor antagonists etanercept (Enbrel), Atrial natriuretic peptide and B-type natriuretic peptide (BNP), Insulin-like growth factor-1 (IGF-1), stromal cell–derived factor-1α (SDF-1), Granulocyte colony–stimulating factor (G-CSF), IL receptor antagonists (tocilizumab), erythropoietin (EPO), Neuregulin (NRG) etc [6]. Sarcomeric protein is the functional unit for myocyte contraction and the cardiomyopathies are caused by mutation in sarcomeric genes. Recent research suggests that stoichiometric replacement of sarcomeric proteins is a potential gene therapy approach to replace mutant proteins, alter sarcomeric responses, or neutralize altered sarcomeric function in cardiac disease.

Alzheimer and other amyloid disease advancement: Protein engineering involves Alzheimer’s research - the most common dementia in older people that start with memory loss and caused by nerve damage in brain. All amyloid diseases such as Parkinson’s, Alzheimer’s have a unique abnormally folded peptide structure/amyloid protein (also called fibrils) [5]. Recently University of Washington’s bioengineers developed a synthetic protein called alpha sheet/affibody protein that complements the toxic structure of amyloid proteins and blocks/neutralizes these proteins to prevent the amyloid fibrils from forming. This approach would be very helpful for diagnosis and specific therapies for Alzheimer’s and other amyloid diseases.

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Biotech World

Sunday, September 18, 2016

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