REVERSING AGING OF THE CENTRAL NERVOUS SYSTEM

Smart overview of the Invention

Engineered nucleic acids, including various expression vectors such as lentiviral, adenoviral, and AAV vectors, are designed to encode specific transcription factors like OCT4, KLF4, and SOX2. These factors are instrumental in cellular reprogramming and tissue regeneration, particularly in the central nervous system. The application also describes recombinant viruses and engineered cells that incorporate these nucleic acids. These components are intended for applications in reversing aging and treating neurological diseases by regulating cellular processes.

Background and Rationale

The application highlights the limited regenerative capacity of mature somatic cells in vital organs, including the brain. Unlike embryonic cells that possess a high regenerative ability, adult somatic cells are prone to aging due to epigenetic changes rather than genetic mutations. The Yamanaka factors (OCT4, SOX2, c-Myc, and KLF4) have been shown to induce pluripotency but pose risks such as tumor formation. Thus, the need for non-toxic methods to reverse cellular aging is emphasized.

Discovery and Implications

Research has pointed out that aging in the central nervous system is primarily driven by epigenetic information loss. This loss affects cellular processes and contributes to aging traits like senescence. Traditional treatments for neurological disorders focus on neurotransmitter modulation rather than addressing cellular aging causes. The application reveals that reprogramming with OCT4, SOX2, and KLF4 can enhance neuronal function without toxic effects.

Innovative Approach

The novel approach involves precise expression of OCT4, SOX2, and KLF4 without c-Myc to promote brain tissue regeneration without toxicity. These transcription factors can cross the blood-brain barrier and reverse brain aging. Expression vectors allow targeted delivery and control of these factors within the central nervous system using high-titer viral vectors like AAVs.

Applications and Potential Benefits

The disclosed systems and methods offer potential for rejuvenating cells in the central nervous system, excluding parts like the retina. The nucleic acids designed for this purpose encode agents that facilitate controlled expression of OCT4, SOX2, and KLF4 without c-Myc involvement. This approach may significantly advance treatments for neurological diseases by addressing cellular aging directly.