Non-viral and viral delivery systems for CRISPR-Cas9 technology in the biomedical field

The clustered regularly interspaced short palindromic repeats(CRISPR)-associated protein 9(CRISPR-Cas9) system provides a novel genome editing technology that can precisely target a genomic site to disrupt or repair a specific gene. Some CRISPR-Cas9 systems from different bacteria or artificial variants have been discovered or constructed by biologists, and Cas9 nucleases and single guide RNAs(sgRNA) are the major components of the CRISPR-Cas9 system. These Cas9 systems have been extensively applied for identifying therapeutic targets, identifying gene functions, generating animal models, and developing gene therapies.Moreover, CRISPR-Cas9 systems have been used to partially or completely alleviate disease symptoms by mutating or correcting related genes. However, the efficient transfer of CRISPR-Cas9 system into cells and target organs remains a challenge that affects the robust and precise genome editing activity. The current review focuses on delivery systems for Cas9 mRNA, Cas9 protein, or vectors encoding the Cas9 gene and corresponding sgRNA. Non-viral delivery of Cas9 appears to help Cas9 maintain its on-target effect and reduce off-target effects, and viral vectors for sgRNA and donor template can improve the efficacy of genome editing and homology-directed repair. Safe, efficient, and producible delivery systems will promote the application of CRISPR-Cas9 technology in human gene therapy.

Recent advances of biomaterials in biotherapy

Biotherapy mainly refers to the intervention and the treatment of major diseases with biotechnologies or bio-drugs,which include gene therapy,immunotherapy(vaccines and antibodies),bone marrow transplantation and stem-cell therapy.In recent years,numerous biomaterials have emerged and were utilized in the field of biotherapy due to their biocompatibility and biodegradability.Generally,biomaterials can be classified into natural or synthetic polymers according to their source,both of which have attracted much attention.Notably,biomaterials-based non-viral gene delivery vectors in gene therapy are undergoing rapid development with the emergence of surface-modified or functionalized materials.In immunotherapy,biomaterials appear to be attractive means for enhancing the delivery efficacy and the potency of vaccines.Additionally,hydrogels and scaffolds are ideal candidates in stem-cell therapy and tissue engineering.In this review,we present an introduction of biomaterials used in above biotherapy,including gene therapy,immunotherapy,stem-cell therapy and tissue engineering.We also highlighted the biomaterials which have already entered the clinical evaluation.

Advances in quantum dot-mediated siRNA delivery

Nano-sized quantum dots（QDs） exhibit uniquely optical properties that are tunable with different sizes and shapes.QDs can emit narrow symmetric bands under a wide excitation range,possess antiphotobleaching stability,and be bio-functionalized on the large surface area.Therefore,QDs are attractive vectors for imaging-guided therapy.Small-interfering RNA（siRNAs）-based therapeutics hold great potential to target a large part of the currently undruggable genes,but overcoming the lipid bilayer to deliver siRNA into cells has remained a major challenge to solve for widespread development of siRNA therapeutics.In this mini-review,we focus on theranostic QD/siRNA assembles for enhancing delivery of siRNA and facilitating evaluation of therapeutic efficacy via imaging of QDs,with special attention to carbonaceous QDs for delivery of siRNA.