Red Biotechnology: A Healthy World

Elsayed I.G.1, a, Kanwugu O.N.1, b, Ivantsova M.N.1, c

Institute of Chemical Engineering, Ural Federal University, Yekaterinburg, Russia

a) Corresponding author: Israa_gaber@yahoo.com

Abstract Biotechnology is an interdisciplinary field of engineering, physics, chemistry and

biology. The present era of Biotechnology has reached to a stage of treating killer diseases like
cancer, HIV; disorders like diabetes, cardiac diseases and even hereditary disease at the genetic
level etc. This review emphasizes the applications of Biotechnology in the medicine field and the
basic development of nanomedicine.
Key words: Transgenics, Xenotransplantation, Nanomedicine, BioPharming, Bio-Printing.
INTRODUCTION
Our awareness of this field has only advanced recently, but it’s been in existence since prehistoric times,
making it one of the oldest technologies to exist, even before the discovery of microbiology (1). Around 4000BC the
ancient Egyptians could already brew beer, ferment cheese and produce baked food (1). By 500BC the Chinese used
moldy soybean curd as the first antibiotic to treat boils (1). During the outbreak of smallpox in the 16 th century,
variolation was practiced in China and then Middle East as a method of Immunization against Smallpox virus (2),
this was before Edward Jenner introduced the first vaccine known to humanity in late 18 th century (3). Thus, the
history of biotechnology was is not a mere scientific fact but rather indicates a human experience passed from a
generation to the next.
In Medicine, biotechnology represented by genetic engineering has greatly advanced through the 20 th
century, since the first successful gene therapy of a 4-year old girl with immune disorder in 1990 (1), to the use of
monoclonal Abs antibodies as immune checkpoint inhibitors in the 21 st century (4). As harmful microorganisms
evolve daily, a revolution in biotechnology was is a must to face every day’s chronic/endemic diseases as well as to
prepare for new ones yet to come. Medical biotechnology uses living organisms or biological molecules to develop
new technologies or products which are beneficial for health. Thus, this makes the application of biotechnology for
diagnosis, prevention and treatment of diseases and disorders to be known as Red Biotechnology. This review will
try to spot the light on some different techniques available nowadays for exploitation in the field of medicine, which
represent both well-established and novel biotechnologies, even if several aspects of their performance are still to be
tested.

TRANSGENICS
Transgenics are considered as a major breakthrough in medical biotechnology, which have emerged due to
multiple and long researches on genetic engineering. Transgenics are usually employed for 2 main reasons;
economical benefits in livestock production, or as models for detecting, diagnosing and treatment of different
diseases (5,6,7). An animal whose genetic material contain a copy of foreign DNA stably integrated into it, is called
a transgenic (5,6). There are many medical fields where transgenics are employed, few of which are
xenotransplantation, biopharming, blood replacement, Recombinant monoclonal antibodies (mAb).

Xenotransplantation

Today, transplantation technology which is the basis for normal life of thousands of patients, is faced with
an acute shortage of appropriate organs. Due to an increasing demand of these organs, xenotransplantation (the
transplantation of organs between discordant species e.g. from animals to human) has emerged. This technique
however has been hit with some major challenges of recent. The use of primates is clouded with some reservations
due to some ethical and moral dilemmas, along with the fear of zoonotic diseases, high cost and slow rate of
breeding, and most species of interest are not only endangered, but they don’t have much work done on their genetic
modification (8). Biotechnology has attempted to solve some of these issues, using transgenics to produce sufficient
and immunologically compatible organs, tissues and cells. Though biotechnology helps to provide organs for
transplantation, major setback of solid organs xenotransplantation is their great immunological incompatibility with
a need for strong immunotherapy, which means low life expectancy and short graft survival. For these reasons,
xenotransplantation is not applicable nowadays for organs, even with transgenic animals (6, 7, 8, 9). Nevertheless,
multiple researches are being conducted to better understand the functionality and heterogenicity of cells through
Single-Cell RNA Sequencing, sophisticated nanotechnology platform and with the help of CRISPR/Cas9 gene
editing technology precisely remove immunogenic molecules while inserting desirable regulatory ones (10).

However, with tissues, the picture is more promising than solid organs and considerable progress has been
achieved, mainly through transgenic pigs, and the introduction of directed immunosuppressive agents. Several
intractable diseases, disorders and injuries are associated with irreversible cell death or aberrant cellular function.
Xenogeneic cells provide several advantages over other approaches, such as implantation at optimal therapeutic
location, possibility for manipulation prior to transplantation to enhance cell function, banking and cryopreservation,
and combination with different cell types in the same graft (i.e. inclusion of phenotypically different cells, inclusion
of immunoprotective cells) (11). Porcine cell transplantation has advanced experimentally and is currently being
used in human clinical trials for treatment of multiple diseases e.g. diabetes, Huntington’s, Parkinson’s etc (6, 11).

BioPharming
In addition, transgenic organisms are used to produce many kinds of proteins which are used
therapeutically for human. These transgenic organisms could be mammal, mammalian cell line, yeast or bacterial
fermentation system. Many therapeutic proteins that were previously harvested from animal tissues are now being
produced as recombinant human proteins. The proteins produced is are less likely to cause allergic response, unlike
the corresponding products extracted from non-engineered animal tissues (6, 13). Most of the biopharmaceuticals
are currently being produced by mammalian cell cultures, mainly using Chinese Hamster Ovarian cell lines (CHO),
as these allows the production of proteins with very similar glycosylation patterns as human protein, followed by E.
coli, then Saccharomyces cerevisiae (12). A variety of recombinant proteins which includes antibodies, vaccines,
blood factors, hormones, growth factors, cytokines, enzymes, milk proteins, collagen, fibrinogen and others are
being developed in transgenic animals (7).
For a large-scale production, protein from mammary gland is the most favorable commercially; due to its
safety, biological activity and low production cost compared to biopharmaceuticals from human tissues. Cows are
likely the most promising animals to be used as transpharmers because they produce large amounts of milk and they
have a longer lifespan than mice or goats. However, working with larger animals, like cattle, is much more
expensive than working with mice, pigs and goat; longer gestation periods, require larger space and consumes more
food. (6, 7, 13). Furthermore, Functional human hemoglobin has been produced in transgenic swine. The transgenic
protein purified from the porcine blood, showed oxygen-binding characteristics like natural human hemoglobin.
Monoclonal, bispecific (14) and polyclonal antibodies are also being produced in serum of cattle. (6, 7)

Blood Replacement

Functional human hemoglobin has been produced in transgenic swine. The transgenic protein purified from
the porcine blood, showed oxygen-binding characteristics like natural human hemoglobin. Monoclonal, bispecific
(14) and polyclonal antibodies are also being produced in serum of cattle. (6, 7)

Recombinant mAb

Recombinant monoclonal antibody is a biopharmaceutical as mentioned above, but It’s not just a protein or
an enzyme that can be bypassed. Multiple procedures of medical analysis and treatment are based only on mAb. Its
production is based on a group of molecular approaches used for the cloning and synthesis of mAb without the use
of conventional tissue culture (hybridoma) method (15). Antibody gene library; which is a collection of
microorganisms transformed with antibody encoding gene fragments from B cells of any source, made it easier for
reproducibility without animal inoculation needed, or B cell harvest waited; besides, they don’t induce anti-murine
response and have a higher specificity (15). When they are conjugated with cytotoxic drugs to target tumor cells,
they are call Anti-Drug Conjugate (ADC) (17); and the latest research is their use as Immune Checkpoint Inhibitors
(4). Furthermore, mAbs are produced in the mammary gland of transgenics. Being too specific made it a
disadvantage from another aspect, so cloned transgenic cattle was developed to produce recombinant bispecific mAb
in their blood (14).
An interesting new development is the generation of trans-chromosomal animals. Trans-chromosomal bovine
offspring were obtained that expressed human immunoglobulin in their blood e.g. coronavirus (MERS-CoV) (16).
Further studies will show whether the additional chromosome will be maintained over future generations and how
stable expression will be. (6, 13)

Examples of therapeutic proteins that are currently in development. (6)

Animal Drug/Protein Use

Goat Human protein C Treatment of thrombosis

Sheep Cftr (Cystic Fibrosis Transmembrane Treatment of cystic fibrosis

Conductance Regulator) 
Sheep, Pig Tissue plasminogen activator Treatment of thrombosis

Sheep, Pig Factor VIII, IX Treatment of hemophilia

Sheep, Cow Fibrinogen Treatment of wound healing

Goat Glutamic acid decarboxylase Treatment of type 1 diabetes

Cow Lactoferrin Treatment of GI tract infection, treatment of

infectious arthritis

NANO-MEDICINE

Nanotechnology has made a revolution in the medical field. In each new medical discovery, side effects on
the body are of major hindrance for its approval. The case is different with nano-medicine, as it works on cellular
level and up, and not the other way around like conventional techniques. It’s applied in the field of treatment,
diagnosis and monitoring of chronic medical cases. So far, not enough data is present on the toxicological aspects of
nanotechnology; that area requires more research on end products of different nanoparticles and their effect on
excretory organs. These are some of their applications in medicine: (18)
Drug Delivery: offers extensive control over delivery location, dosage, and drug release characteristics. Not only
offers delivery to specific cells but allows cell wall permeation for drugs and bioactive macromolecules; which need
intracellular delivery for its bioactivity. (18, 19, 20)
Nano-vaccines: conventional vaccine depends on the delivery of antigen to immune cells. Mucosal vaccination is
usually face by degradation of vaccine or limited uptake by cells. Encapsulation of vaccine has enhanced the
delivery and the immune response wanted. (18)
Gene Delivery: is a form of non-viral vectors e.g. Nano particles. So genetic disorders would be easily resolved
through insertion of a missing gene, swapping of faulty gene for a normal one or repairing abnormal gene by
selective reverse mutation. (18, 19)
Nanorobotics: they function as minute devices, present in the body for constant monitoring of body functions and
acquisition of patient’s data to improve treatment efficiency and early diagnosis of possibly serious diseases.
Furthermore, they would advance biomedical intervention with minimally invasive surgeries. (18, 19, 20)

3D BIOPRINTING
 This revolutionary technology can produce bioartificial organs automatically mimicking their natural
counterparts using heterogeneous stem cell types and other biomaterials. There are 5 major types of 3D-bioprinting
technologies; inkjet-based bioprinting, extrusion-based bioprinting, laser-assisted bioprinting, stereolithography-
based bioprinting and microvalve-based bioprinting (22). Regardless, aAll types of bioprinting require a 3D printer,
3D model file, bioink (consisting of biomaterials, bioactive components and cells) and print platform. Bioprinter
builds layers of tissues vertically to create 3D structure, outputting cell-laden, viscoelastic hydrogel called bioink to
support and protect cells, and forms a matrix for cell growth (24). The technique has already been applied in the
printing of skin, cardiac and skeletal muscles, and cartilage and bone tissue. It can also be used for generation of
different tissue cultures for research purposes. Bioprinting of solid organs e.g. heart, liver, kidney needs more
research to be conducted, because of their complex 3D structure. (22, 23, 24)

CONCLUSION
Red biotechnology is futuristic in all aspects. The 20th century was the golden age for Red biotechnology,
with many discoveries that led from one to another. Nowadays, transgenic are broadly used for increased
production; but in the future, therapeutic production would be more cognitive. With more research on different
applications of red biotechnology, Medicine will be much easier, and life would be longer. Even though animals can
not be denied their major attribution to that sector, some ethical and moral issues are considered as a set back for
further studies. The cost of scientific research and time-consuming clinical trials are an everlasting dilemma for all
researchers. Red biotechnology has quickly evolved and gone a long way in over a century, which is a short time for
the history of humanity. So, I believe we can do much more in the near future.

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