JOURNAL OF TROPICAL LIFE SCIENCE 2020, Vol. 10, No. 2, 163 – 173 http://dx.doi.org/10.11594/jtls.10.02.09 How to cite: Fallahi S, Mohammadhassan R (2020) A Review of Pharmaceutical Recombinant Proteins and Gene Transformation Approaches in Transgenic Poultry. Journal of Tropical Life Science 10 (2): 163 – 173. doi: 10.11594/jtls.10.02.09. Review Article A Review of Pharmaceutical Recombinant Proteins and Gene Transformation Approaches in Transgenic Poultry Sepideh Fallahi 1 , Reza Mohammadhassan 2 1 Animal Science Department, Amino Techno Gene Private Virtual Lab (NGO), Tehran 1495845983, Iran 2 Plant Science Department, Amino Techno Gene Private Virtual Lab (NGO), Tehran 1495845983, Iran Article history: Submission September 2019 Revised January 2020 Accepted February 2020 ABSTRACT Transgenic animals are employed to synthesize pharmaceutical recombinant proteins for three decades. There are many problems to use farm mammalian animals for recombinant production such as high cost of production and maintenance, long generation interval, toxic effects of some human-source pharmaceutical proteins in other mammalian and incompatibility of human-source glycosylation with the other mammalian' glycosylation that all lead to low efficiency. Thus, transgenic poultry has been considered as the bioreactor of recombinant protein production. Increasing demand for pharmaceutical human proteins caused to make considerable efforts to develop transgenic poultry producing eggs contain recombinant protein. In the present review, at the first, transgenic animal and poultry are compared for their benefits and limitations. Then, the protein content of the egg, the features, gene and promoter of the egg are studied. After that, the recent achievements of the producing pharmaceutical recombinant proteins are considered. In the following, there are some explanations about gene transformation approaches in poultry, including sperm-, testis-, PGCs, and blastocyst-mediated methods depending on CRISPR/Cas9, Retroviral vectors, and DNA microinjection techniques, and embryonic manipulation approaches such as windowing and Ex ovo for introducing and injecting transformed cells into eggs. Keywords: Transgenic Poultry, Bioreactor, Pharmaceutical Recombinant Pro- teins, Transgenic Egg, Human-Source Protein Drugs, Poultry Transformation *Corresponding author: E-mail: sepide.fallahi@gmail.com Introduction Transgenic animals can be employed as biore- actors to produce pharmaceutical proteins. Re- combinant DNA technology has fundamentally been made changes to produce pharmaceutical proteins [1]. In gene transformation, a DNA frag- ment encoding a protein is digested by restriction enzymes then ligated to a vector digested by the same enzymes [2]. According to length of the tar- get gene, there are several vectors. In addition to the target gene, each vector includes a promoter and a reporter gene. After constructing a vector, it is transferred to a single cell. Then the cell is cul- tured in specific medium to grow and divide. This process causes to replicate the gene. Simultane- ously, the replicated genes are expressed to pro- duce a lot of the recombinant proteins. After that, these proteins are extracted from the cells [3]. Dis- armed viruses can be used as vectors as an ideal system to transform poultry; because they can eas- ily and cheaply multiply to enhance target protein synthesis. Moreover, they facilitate the protein pu- rification more efficiently. There are three promi- nent approaches to transform animals; using bac- teria, fungi and mammalian cell, nevertheless, none of them are as effective as virus [4]. Bacterial system, such as Escherichia coli which can easily and rapidly multiply and produce protein, needs huge budget that prevents pervasive development. On the other hand, bacteria are not susceptible to produce complex protein components rapidly and make Post-translation modification to activate proteins biologically [1]. Fungi system, such as