This past Friday the governing Board of the California Institute for Regenerative Medicine (CIRM) approved two additional discovery research projects as part of the $5 million in emergency funding for COVID-19 related projects. This brings the number of COVID-19 projects CIRM is supporting to 15, including three clinical trials.
The Board awarded $249,999 to Dr. Evan Snyder at the Sanford Burnham Prebys Medical Discovery Institute. The study will use induced pluripotent stem cells (iPSCs), a type of stem cell that can be created by reprogramming skin or blood cells, to create lung organoids. These lung organoids will then be infected with the novel coronavirus in order to test two drug candidates for treatment of the virus. The iPSCs and the subsequent lung organoids created will reflect diversity by including male and female patients from the Caucasian, African-American, and Latinx population.
This award is part of CIRM’s Quest Awards Program (DISC2), which promotes promising new technologies that could be translated to enable broad use and improve patient care.
The Board also awarded $150,000 to Dr. Steven Dowdy at UC San Diego for development of another potential treatment for COVID-19.
Dr. Dowdy and his team are working on developing a new, and hopefully more effective, way of delivering a genetic medicine, called siRNA, into the lungs of infected patients. In the past trying to do this proved problematic as the siRNA did not reach the appropriate compartment in the cell to become effective. However, the team will use an iPSC lung model to help them identify ways past this barrier so the siRNA can attack the virus and stop it replicating and spreading throughout the lungs.
This award is part of CIRM’s Inception Awards Program (DISC1), which supports transformational ideas that require the generation of additional data.
A supplemental award of $250,000 was approved for Dr. John Zaia at City of Hope to continue support of a CIRM funded clinical study that is using convalescent plasma to treat COVID-19 patients. The team recently launched a website to enroll patients, recruit plasma donors, and help physicians enroll their patients.
“The use of induced pluripotent stem cells has expanded the potential for personalized medicine,” says Dr. Maria T. Millan, the President & CEO of CIRM. “Using patient derived cells has enabled researchers to develop lung organoids and lung specific cells to test numerous COVID-19 therapies.”
The Stem Cellar 
The study of using induced pluripotent stem cells(iPSCs) by reprogramming of skin or blood into lung organoids provide an experimental model to see the effects of drugs after Covid-19 infection. Lung organoids are not mature cells but a group of early cultures. The mature cells are active, adherence and functioning cells. The outer surface of the cells always displays diversity types and levels of cellular molecules and receptors, but those characteristic features are not seen in early cells. In addition, the intracellular of signalling pathway in mature cells are more complex and integrated in cells. The results of drugs treatment on early and mature cells after Covid-19 infection might produce different response. For instance, the lung of children have less of ACE-2 receptors than the lung of adults which produce higher levels of the receptors. Therefore, majority of adults are hit hard by Covid-19 infection. It can be concluded that the model of iPSCs only provide limited insights of pathogenic cellular response of Covid-19 infection. It cannot be used as a representative model to study the organs and tissues of human.
The pandemic of Covid-19 cause millions of human’s lives lost in the world. Recently, WHO reported that the existent of mutated strain of Covid-19 which was so called G614D cause major outbreak in US and Europe. The new strain of virus has the most highest infection rate to cause millions and millions of patients come down from virus infection. The issue of mutation in Covid-19 gives the world a big blow to the effort for vaccine development. However, the new therapeutic approach of using siRNA to intervene the replication of virus in host cell provides a new lease of life to Covid-19 infected patient. Covid-19 has high infection rate, both intravenous and intracuenous injection of high clinical dosage of siRNA to an individual might end up with undesirable of toxicology effect due to siRNA blocking normal cells from functioning. Antibody and monoclonal antibody specific toward molecular antigen of virus, can be coupled with siRNA to effectively halt the replication cycles of viruses. There are 4 main structures of protein coat in Covid-19 , which included proteins spike, envelope, membrane and nucleocapsid. Covid-19 also encodes special structures and asscessory proteins(HE protein, 3a/b proteins & 4a/b proteins) to maintain the integrity of virus genome and structure for binding and replication. The spike proteins of Covid-19 bind to cellular ACE-2 before hijacking into infected cell. Before binding to cellular attachment of ACE-2, spike protein has to be primed by protease TMPRSS2. The replication and transcription of Covid-19 takes place at cytoplasmic membrane of host cell. Therefore, antibodies coupled-siRNA targeted to viral molecular structures or protease can be more effective to intervene the replication of virus.
Convalescent plasma is an alternative choice of treatment for Covid-19 infected patients. However, patients with different virus strains may hinder the effectiveness of neutralizing antibodies.