SENOLYTIC CRISPR CAR T CELLS PRODUCED BY CRISPR-CAS9 GENOME EDITING

Smart overview of the Invention

Chimeric Antigen Receptor (CAR) T cell therapies are innovative treatments that engineer T cells to target specific cell surface proteins, allowing for a more effective immune response against various diseases. By redirecting T cell specificity, these therapies can address conditions such as cancer and infectious diseases. Recent advancements have focused on utilizing CAR T cells to target senescent cells, which are linked to age-related pathologies and chronic inflammation.

Application of CRISPR-Cas9 in CAR T Cells

Utilizing CRISPR-Cas9 technology, researchers can enhance the potency and specificity of CAR T cells by integrating a chimeric antigen receptor gene directly into the genome of T cells. This method involves a homology-directed repair (HDR) template that allows for precise gene editing, promoting the development of CAR T cells that can effectively target the urokinase Plasminogen Activator Receptor (uPAR) found on senescent cells.

Targeting Senescent Cells

Senescent cells contribute to tissue dysfunction and age-related diseases by secreting inflammatory factors that attract immune cells. By engineering CAR T cells to target uPAR, this approach seeks to eliminate these problematic cells, potentially alleviating symptoms associated with neurodegenerative diseases like Alzheimer's and Parkinson's. The goal is to create therapies that can effectively reduce the burden of senescent cells in aging populations.

Methods for Producing CAR T Cells

The described methods involve preparing an HDR template and using a Cas9 ribonucleoprotein complex to introduce the CAR gene into the T cell genome. This process allows for the generation of a cultured population of CAR T cells that express the transgene driven by endogenous or included promoters. The resulting CAR T cells are designed to bind specifically to uPAR, facilitating the targeted elimination of senescent cells.

Potential Applications and Benefits

The development of senolytic CAR T cell therapies holds promise for treating a range of conditions associated with aging and cellular senescence. By leveraging CRISPR-Cas9 technology, these therapies can provide a more effective means of addressing neurodegenerative diseases and improving overall tissue health in elderly individuals. This innovative approach may lead to significant advancements in regenerative medicine and age-related treatments.