mRNA vaccines represent a promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. However, their application has until recently been restricted by the instability and inefficient in vivo delivery of mRNA. Recent technological advances have now largely overcome these issues, and multiple mRNA vaccine platforms against infectious diseases and several types of cancer have demonstrated encouraging results in both animal models and humans. This Review provides a detailed overview of mRNA vaccines and considers future directions and challenges in advancing this promising vaccine platform to widespread therapeutic use.

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mRNA vaccines — a new era in vaccinology

During the last two decades, there has been broad interest in RNA-based technologies for the development of prophylactic and therapeutic vaccines. Preclinical and clinical trials have shown that mRNA vaccines provide a safe and long-lasting immune response in animal models and humans. In this review, we summarize current research progress on mRNA vaccines, which have the potential to be quick-manufactured and to become powerful tools against infectious disease and we highlight the bright future of their design and applications.

/pdf/advances-in-mrna-vaccines-for-infectious-diseases-46t6tx0379.pdf

Advances in mRNA Vaccines for Infectious Diseases.

Neurofibromatosis type 2

The therapeutic use of messenger RNA (mRNA) has fueled great hope to combat a wide range of incurable diseases. Recent rapid advances in biotechnology and molecular medicine have enabled the production of almost any functional protein/peptide in the human body by introducing mRNA as a vaccine or therapeutic agent. This represents a rising precision medicine field with great promise for preventing and treating many intractable or genetic diseases. In addition, in vitro transcribed mRNA has achieved programmed production, which is more effective, faster in design and production, as well as more flexible and cost-effective than conventional approaches that may offer. Based on these extraordinary advantages, mRNA vaccines have the characteristics of the swiftest response to large-scale outbreaks of infectious diseases, such as the currently devastating pandemic COVID-19. It has always been the scientists' desire to improve the stability, immunogenicity, translation efficiency, and delivery system to achieve efficient and safe delivery of mRNA. Excitingly, these scientific dreams have gradually been realized with the rapid, amazing achievements of molecular biology, RNA technology, vaccinology, and nanotechnology. In this review, we comprehensively describe mRNA-based therapeutics, including their principles, manufacture, application, effects, and shortcomings. We also highlight the importance of mRNA optimization and delivery systems in successful mRNA therapeutics and discuss the key challenges and opportunities in developing these tools into powerful and versatile tools to combat many genetic, infectious, cancer, and other refractory diseases. 

/pdf/mrna-based-therapeutics-powerful-and-versatile-tools-to-2wrggsl0.pdf

mRNA-based therapeutics: powerful and versatile tools to combat diseases

The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2

Objective Describe the changes in hearing ability and progression of disease over time in subjects with neurofibromatosis Type 2 enrolled in a multicenter natural history study of vestibular schwannomas in neurofibromatosis Type 2. Study design Retrospective clinical study. Setting International neurofibromatosis Type 2 tertiary care centers. Patients Study participants had a clinical diagnosis of neurofibromatosis Type 2, at least one untreated vestibular schwannoma, and were at least 5 years old. Sixty-three subjects (108 ears) with audiology data at either short-term follow-up (7 mo-2 yr) or long-term follow-up (3-5 yr) after diagnosis were examined in this study. Main outcome measures Changes in four-frequency pure-tone average and speech discrimination score before any treatment intervention for both follow-up intervals. Results Within 2 years of the diagnosis of neurofibromatosis Type 2, 27% of the ears experienced a significant loss in pure-tone average relative to diagnosis, and 73% of the ears experienced no significant change in hearing. Conclusion Newly diagnosed neurofibromatosis Type 2 patients who do not require immediate treatment of both vestibular schwannomas are likely to have stable hearing in the unoperated ear(s) for approximately 1 to 2 years.

Hearing changes after diagnosis in neurofibromatosis type 2.

OBJECTIVE: To determine whether congenitally deafened adults achieve improved speech perception when auditory and visual speech information is available after cochlear implantation. STUDY DESIGN: Repeated-measures single subject analysis of speech perception in visual-alone, auditory-alone, and audiovisual conditions. SETTING: Neurotologic private practice and research institute. SUBJECTS: Eight subjects with profound congenital bilateral hearing loss who underwent cochlear implantation as adults (aged 18-55 years) between 1995 and 2002 and had at least 1 year of experience with the implant. MAIN OUTCOME MEASURES: Auditory, visual, and audiovisual speech perception. RESULTS: The median for speech perception scores were as follows: visual-alone, 25.9% (range, 12.7-58.1%); auditory-alone, 5.2% (range, 0-49.4%); and audiovisual, 50.7% (range, 16.5-90.8%). Seven of eight subjects did as well or better in the audiovisual condition than in either auditory-alone or visual-alone conditions alone. Three subjects had audiovisual scores greater than what would be expected from a simple additive effect of the information from the auditory-alone and visual-alone conditions alone, suggesting a superadditive effect of the combination of auditory-alone and visual-alone information. Three subjects had a simple additive effect of speech perception in the audiovisual condition. CONCLUSION: Some congenitally deafened subjects who undergo implantation as adults have significant gains in speech perception when auditory information from a cochlear implant and visual information by lipreading is available. This study shows that some congenitally deafened adults are able to integrate auditory information provided by the cochlear implant (despite the lack of auditory speech experience before implantation) with visual speech information.

Improved speech perception in adult congenitally deafened cochlear implant recipients.

Results of a randomized, placebo-controlled clinical trial of famvir for active Meniere's disease

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Hearing changes after diagnosis in neurofibromatosis type 2.

Improved speech perception in adult congenitally deafened cochlear implant recipients.

Results of a randomized, placebo-controlled clinical trial of famvir for active Meniere's disease