Future of genetic therapies for rare genetic diseases: what to expect for the next 15 years?

Abstract

Introduction: Rare genetic diseases affect millions of people worldwide. Most of them are caused by defective genes that impair quality of life and can lead to premature death. As genetic therapies aim to fix or replace defective genes, they are considered the most promising treatment for rare genetic diseases. Yet, as these therapies are still under development, it is still unclear whether they will be successful in treating these diseases. This study aims to address this gap by assessing researchers’ opinions on the future of genetic therapies for the treatment of rare genetic diseases. Methods: We conducted a global cross-sectional web-based survey of researchers who recently authored peer-reviewed articles related to rare genetic diseases. Results: We assessed the opinions of 1430 researchers with high and good knowledge about genetic therapies for the treatment of rare genetic diseases. Overall, the respondents believed that genetic therapies would be the standard of care for rare genetic diseases before 2036, leading to cures after this period. CRISPR-Cas9 was considered the most likely approach to fixing or replacing defective genes in the next 15 years. The respondents with good knowledge believed that genetic therapies would only have long-lasting effects after 2036, while those with high knowledge were divided on this issue. The respondents with good knowledge on the subject believed that non-viral vectors are more likely to be successful in fixing or replacing defective genes in the next 15 years, while most of the respondents with high knowledge believed viral vectors would be more successful. Conclusion: Overall, the researchers who participated in this study expect that in the future genetic therapies will greatly benefit the treatment of patients with rare genetic diseases. Plain Language Summary A global survey of researchers on the future of genetic therapies for rare genetic diseases Rare genetic diseases are caused by defective genes that result from one or more mutations in the genome. Today, the therapeutic options for these diseases are limited, and there are approved treatments for about 5% of them. In the future, genetic therapies (a group of techniques developed to correct defective genes) are expected to revolutionize the treatment of rare genetic diseases. Although promising, most of these therapies are currently under development and have a long way to go before their efficacy and safety can be proved. The uncertainty surrounding this topic therefore means the success of genetic therapies in treating or curing rare genetic diseases is not yet assured. To address this knowledge gap, we surveyed 1430 researchers working in rare genetic diseases about the future of genetic therapies for the treatment of these diseases over the next 15 years. Most of them expected gene therapies to be the standard of care for rare genetic diseases before 2036 and to be able to cure them after this date. CRISPR-Cas9 was felt to be the gene editing approach that was most likely to succeed in fixing or replacing defective genes in the next 15 years. The respondents with high knowledge about gene therapies for the treatment of rare diseases believed gene therapies would have long-lasting effects before 2036, while those with good knowledge expected this to be the case only after 2036. The former believed in viral vectors and the latter in non-viral vectors to fix or replace defective genes in the next 15 years.

Why the way we define diseases prevents innovation and precision medicine

“…This may start off with ICD to ensure buy-in from as many clinicians as possible. Evidence that complex disease phenotypes will benefit from molecular definitions and subtypes comes from the 7,000 rare diseases most of which are named after the responsible gene or protein 75 , providing both a precise diagnosis and options for a curative strategy 76 . To reduce expert mapping workload, eventually, automatic ontology curation with similarity-based reasoning may be employed.…”

Benefits and Risks of Sharing Genomic Data for Research: Comparing the Views of Rare Disease Patients, Informal Carers and Healthcare Professionals

“…This will likely help to clarify what are reasonable expectations from genomics research, thus rendering communication between all parties more fluid, transparent and dependable. Genomics research will not necessarily translate into the delivery of individual therapeutic benefits in the short-run, but rather into a set of discoveries that may impact patients’ personal health outcomes in the future [ 37 , 38 , 39 ]. Nevertheless, access to this information is unlikely to discourage patients and their informal carers from sharing genomic data.…”

Insights into the Mechanism of CRISPR/Cas9-Based Genome Editing from Molecular Dynamics Simulations

“…9 − 11 Thus, CRISPR-based technology appears to be a promising approach for correcting genetic defects in the coming decades. 12 …”

“…9−11 Thus, CRISPR-based technology appears to be a promising approach for correcting genetic defects in the coming decades. 12 Advancements in the structural study and the development of cutting-edge computer technology with ever-increasing computational power have opened the possibility of performing structure-based computational analysis. 13,14 MD simulations have been a popular method for understanding the dynamics of biomolecules at a molecular level by extensive exploration of phase space.…”

“…Although this germline gene editing in humans raised ethical concerns, the immense potential of CRISPR/Cas9 in curing genetic disease and thus improving human life in the future is undeniable. One of the recent breakthroughs in CRISPR/Cas9 technology was the development of the CRISPR-based drug CTX001 to cure sickle cell disease (SCD) and β-thalassemia. − Thus, CRISPR-based technology appears to be a promising approach for correcting genetic defects in the coming decades …”