Transient delivery of modified mRNA encoding TERT rapidly extends telomeres in human cells

Area of Science:

• Cell Biology
• Molecular Biology
• Biotechnology

Background:

• Telomere extension is crucial for cell culture, tissue engineering, and disease treatment.
• Nonviral, non-integrating methods for telomere extension are currently inefficient.

Purpose of the Study:

• To investigate the efficacy of modified mRNA encoding telomerase reverse transcriptase (TERT) for transient telomere extension.
• To assess the impact of this method on cell proliferation and senescence in human fibroblasts and myoblasts.

Main Methods:

• Delivery of modified mRNA encoding TERT to human fibroblasts and myoblasts.
• Multiple transfections over a 4-day period.
• Assessment of telomere length, telomerase activity, population doublings, and senescence markers.

Main Results:

• Transient increase in telomerase activity (24-48 h) and rapid telomere extension (up to 0.9 kb).
• Significant increase in cell proliferative capacity (population doublings) in a dose-dependent manner.
• Identification of a transient refractory period between transfections, followed by restored responsiveness.

Conclusions:

• Modified mRNA delivery of TERT offers a rapid, non-integrating method for telomere extension and increased cell proliferation.
• This approach enhances cell number significantly without insertional mutagenesis risk.
• Treated cells eventually senesce, similar to controls, indicating safety for applications in disease modeling, drug screening, and regenerative medicine.