SynBio7: SynBio and Regenerative Medicine (v1.0)

Regenerative medicine deals with the "process of replacing, engineering or regenerating human or animal cells, tissues or organs to restore or establish normal function". This field holds the promise of engineering damaged tissues and organs by stimulating the body's own repair mechanisms to functionally heal previously irreparable tissues or organs. 

The US regenerative medicine market is poised for significant expansion. primarily fueled by increased government funding (like NIH and BARDA) and favorable regulatory policies. Moreover, private investments and partnerships between biotech companies and research institutions have also played a vital role. As a leading global player in this field, the US is at the forefront of R&D with numerous groundbreaking therapies and treatments being developed and commercialized. 

Although great strides have been made to prolong life, we have not yet mastered ways to improve it. We often spend the last decade of our life with chronic conditions like Alzheimer, diabetes, back pain, etc. In this essay, we will particularly look at developments in repair of hearing, and new efforts to address aging and longevity, and also touch on tissue and organ/organoid engineering applying SynBio. 

In the bio7 essay, I talk about how hearing works. A third of seniors suffer some degree of hearing loss. Many young people also have some hearing loss due to exposure to high noise levels from ear buds and other devices. There are also other causes including genetic. A genetic disorder is an area where synthetic biology - more specifically gene therapy - could help. Usher syndrome is a condition that results in hearing loss as well as blindness. Individuals with Ushers syndrome are born with it but are often diagnosed as children or teenagers. It accounts for half of cases where children are both blind and deaf. There are a number of companies working on a solution. Editas medicine founded by Nobel winner Jennifer Doudna as well as famed biologists George Church and Feng Zhang are working on a gene therapy solution (gene therapy is a subfield of SynBio). It may also help restore the sight. The potential is enormous. 

The study of ageing has become an increasingly fertile field of research. The more we understand normal ageing, the more synthetic biologists have opportunities to assist. There are several proposed mechanisms for cellular ageing. 

1. Cells reach a point called cellular senescence where they cease to divide.
2. Mitochondrial disfunction is where the cellular organ that produces energy no longer works properly. 
3. Loss of proto stasis is disruption of the precise coordination between molecular machineries assisting a protein from its conception to demise. 
4. Epigenetic alterations are age-related changes in gene expression that harm the fundamental functions of cells.  
5. Telomere attritions limits the number of times our cells can divide, leading to dwindling populations of cells in vital organs. 
6. Genomic instability is where the genome undergoes frequent mutations. 
7. Altered intercellular communication is the change in signals between cells that can lead to some of the diseases and disabilities of aging.  
8. and finally Stem cell exhaustion is where stem cell numbers decline, and their capacity for renewal diminishes. 

Synthetic biology scientists are doing research to try to engineer longevity in Cells. Around 2020, a group of researchers at the University of California San Diego identified two distinct directions that cells follow during aging. These processes can be likened to a car aging either due to engine deterioration or transmission wear, but not both simultaneously. Building upon this knowledge, they genetically manipulated these processes to extend the lifespan of cells. Recently, they took this research a step further using synthetic biology. They engineered a solution that prevents cells from reaching their normal levels of deterioration associated with aging. How did they achieve this? By creating a biosynthetic ‘clock’ that keeps cells cycling between two detrimental “aged” states. This gene oscillator periodically switches the cell’s aging mechanism, avoiding prolonged commitment to either pathway thereby slowing cell degeneration. This was however just a proof of concept. 

Tissue engineering is a ripe area of research. Synthetic biology is being applied to this field. Tissue engineering aims to restore, maintain, improve, or replace various types of biological tissues. Synthetic biology today is aimed mainly at engineering cells so that they can perform custom functions. Applying synthetic biological approaches to tissue engineering may be one way of engineering custom structures. Scientists also design and develop inexpensive and effective biosensors, and biomaterials for implants with SynBio.   

 

At any given time, there are 70 to 100 thousand people on the national organ transplant list. Many die waiting for a doner. The first kidney transplant was 1954. The first liver and lung transplant were 1963. The first pancreas transplant was 1966. The first heart transplant was 1967. The first bone marrow transplant was the 1970's. The first transplant of umbilical cord blood was 1988. Organoids are tiny, three-dimensional tissue cultures derived from stem cells. They open the possibility of creating individualized, complex collections of cells that bear a resemblance to a patient’s own tissues.  Organ and organoid engineering are extraordinarily complex, and this essay will not cover that but there is active SynBio research in that area.